Back To Basics Practical Neurology

Practical Neurology
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Back to basics: syndromic approach to neurological
diagnosis.
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Journal: Practical Neurology
Manuscript ID Draft
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Article Type: Review
Date Submitted by the

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Author:
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Complete List of Authors: Galnares-Olalde, Javier; Instituto Nacional de Neurologia y Neurocirugia

Manuel Velasco Suarez, Neurology
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Medina-Rioja, Raul; Instituto Nacional de Neurologia y Neurocirugia

Ramirez-Esquivel, David; Instituto Nacional de Neurologia y Neurocirugia
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Saldívar-Dávila, Sergio; Instituto Nacional de Neurologia y Neurocirugia

Jorge de Sarachaga, Adib; Instituto Nacional de Neurologia y
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Neurocirugia Manuel Velasco Suarez, Neurology

Alvarado-Bolaños, Alonso; Instituto Nacional de Neurologia y
Neurocirugia Manuel Velasco Suarez, Neurology
López-Hernández, Juan; Instituto Nacional de Neurologia y Neurocirugia
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Keywords: CLINICAL NEUROLOGY

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https://mc.manuscriptcentral.com/pn
Page 1 of 40 Practical Neurology
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Practical Neurology Page 2 of 40
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3 Title
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5 Back to basics: syndromic approach to neurological diagnosis.
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11 Authors:
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13 Galnares-Olalde Javier Andrés
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Medina-Rioja Raúl
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16 Ramirez-Esquivel David Ubaldo
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18 Saldívar-Dávila Sergio
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20 Jorge-de-Saráchaga Adib
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22 Alvarado-Bolaños Alonso Alejandro

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24 López-Hernández Juan Carlos
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29 1Department of Neurology, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez,
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31 Mexico City, Mexico.
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Correspondence
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49 Correspondent author: Galnares-Olalde Javier Andrés
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51 Mail Address: j_galnareso@hotmail.com
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60 https://mc.manuscriptcentral.com/pn
1
2
3 Introduction
4
5 In neurology, not all diseases are straight-forward clinical diagnoses. Some of them represent a
6 diagnostic challenge, even for experienced neurologists. Neurological diagnosis since the 19th
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century has a central objective: localization. A syndromic diagnostic approach is useful to guide
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9 patient’s workup in complex cases, especially directing ancillary testing.
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11 Moreover, an adequate nomenclature is helpful for a proper communication between clinicians.
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12 Nomenclature is different depending the bibliography or “common use” terminology. The present
13 article reviews the principal neurological syndromes and nomenclature.
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17 Neurological syndromes
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19 Encephalopathic syndrome
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Encephalopathy is defined as an acute or subacute change in mental status, which may include
21
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22 change in alertness, altered cognition and change in personality or behavior, usually less than 4
23 weeks. Other terms that are commonly misused to define encephalopathy are acute confusional
24 state, acute brain dysfunction or organic brain syndrome. Also, it is usually a term that may be
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25 confused with delirium. Encephalopathy is mostly used by neurologists or internal medicine

26
specialists, while delirium is generally used by psychiatrists, intensivists, anesthesiologists, and
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28 gerontologists. (1)
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Delirium refers to a clinical state characterized by a combination of features defined by diagnostic
or
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31 systems such as DSM-V, International Statistical Classification of Diseases and Related Health
32 Problems (ICD-11), or Cognitive Assessment Method (CAM). They consider as criteria for delirium
33 an acute onset of altered mental status, a fluctuating course, inattention, and disorganized thinking.
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(2,3) The problem of defining delirium is that some scenarios do not fulfill the diagnostic criterion,
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36 such as subtle cases of decreased level of consciousness or subsyndromal delirium. Encephalopathy
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37 includes those clinical presentations (subsyndromal delirium, delirium per se or decreased level of
38 consciousness). In neurological approach, we suggest using only the terms encephalopathy and
39 delirium, and avoid using acute confusional state, acute brain dysfunction or organic brain
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syndrome.
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42 Encephalopathy traduces diffuse cortical dysfunction, making localization nonspecific. Underlying
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causes of encephalopathy include both primary neurologic and systemic conditions, having a broad
45 and complex differential diagnosis. (4) A useful guide to organize or to approach encephalopathy is
46 by temporal evolution, as proposed by Erkkinen et al (5) (Table 1).
47
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48 Hyperacute Acute Subacute Chronic

49 Primary -Vascular (IS, ICH) -Vascular (SDH) -Vascular (SDH) -Vascular (SDH)
50 neurologic -Seizure -Inflammatory -Neoplasm related -Degenerative
51 -Migraine (acute (brain tumors or -NPH
52 -Trauma demyelination) paraneoplastic) -Infectious (syphilis,
53 -Infectious (bacterial -Inflammatory HIV neurocognitive
54 or viral meningitis -Infectious (fungal, disease)
55 and encephalitis) Tb, Parasitic,
56 complications of HIV)
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1
2
3 Systemic -Hypertensive -Systemic infection (any) -Heart failure
4 encephalopathy -Toxic/metabolic/drug related -Endocrinopathy
5 -Psychiatric -Malignancy
6 -Autoimmune
7 -Obstructive sleep
8 apnea
9 Table 1. Selected causes of encephalopathy divided by time course. HIV = human
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immunodeficiency virus; ICH = intracranial hemorrhage, includes subarachnoid, subdural, epidural,
11
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12 intraparenchymal; IS = ischemic stroke; NPH = normal pressure hydrocephalus; OSA = obstructive
13 sleep apnea; SDH = subdural hematoma; TB = tuberculosis. Obtained from Erkkinen et al.
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17 Encephalitic syndrome
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Encephalitis is defined as inflammation of the brain parenchyma associated with neurologic
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20 dysfunction. (6) It is strictly a pathologic diagnosis, nonetheless, a biopsy is rarely done due to
21 comorbidities associated with neurosurgical procedure. For this reason, encephalitis has been
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22 defined by clinical, imaging, and electroencephalographic criterion. (7) Venkatesan et al proposed a

23 case definition of an encephalitic syndrome (for both infectious and autoimmune causes), based on
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the following: (8)

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26 ● Mayor criterion (required):
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o Patients presenting to medical attention with altered mental status (defined as
29 decreased or altered level of consciousness, lethargy, or personality change) lasting
or
30 ≥24 h with no alternative cause identified.

31 ● Minor criteria (2 required for possible encephalitis; ≥3 required for probable or confirmed
32 encephalitis):
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34 o Documented fever ≥38° C (100.4°F) within the 72 h before or after presentation

35 o Generalized or partial seizures not fully attributable to a preexisting seizure disorder
36 o New onset of focal neurologic findings
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37 o CSF pleocytosis (WBC count ≥5/cubic mm)

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o Abnormality of brain parenchyma on neuroimaging suggestive of encephalitis that
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40 is either new from prior studies or appears acute in onset
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41 o Abnormality on electroencephalography that is consistent with encephalitis and not

42 attributable to another cause.
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44 As in the case of encephalopathy, localization is nonspecific in encephalitis, as it represents a diffuse

45 cortical condition. Main causes include viruses, small intracellular bacteria that directly infect the
46 brain parenchyma and some parasites. It can also occur without direct brain infection, as in acute
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disseminated encephalitis myelitis (ADEM), or antibody-associated encephalitis. (9)
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51 Altered consciousness syndromes
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53 Consciousness is defined as the state of full awareness of the self and one’s relationship to the
54 environment. According to Plum & Posner, the level of consciousness of a patient is defined at the
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56 bedside by the responses of the patient to the examiner. (10)
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3 Although there are different classifications found in the literature, we prefer using the following
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terms which we find practical for clinical description:
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6 ● Awake or conscious: the patient is aware of himself and his environment.
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● Obtundation: condition in which a patient presents a mild reduction in alertness, or
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9 interaction with the environment. He/she may seem drowsy and respond to verbal
10 instructions.
11 ● Stupor: condition of behavioral unresponsiveness, in some cases referred as simulating
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12 “deep sleep”. The patient shows no response to verbal responses, only to pain stimuli.
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● Coma: condition of total unresponsiveness, even to noxious stimuli.
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As mentioned previously, an altered consciousness syndrome may be considered as part of
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17 encephalopathy. Nonetheless, in conditions such as epilepsy or herniation syndromes, altered
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18 consciousness pathophysiology is different. Thus, this syndrome should be defined according to its
19 accompanying clinical features to orient clinical approach. (11)
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21 Localization of altered consciousness syndromes depends on the clinical context. In case of altered
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22 consciousness as part of encephalopathy or seizure, there is no specific localization. If part of

23 herniation syndromes, it may imply a lesion is compressing the ascending arousal system or
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distorting brain tissue so that secondarily compresses components of the forebrain or ascending
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26 arousal system. These processes may indicate a tumor, hematoma, or abscess. For destructive
27 lesions to cause coma, they need to affect the diencephalon or brainstem bilaterally. Examples of
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28 these are hemorrhage, infarction, trauma, or infection. (12)

29
or
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32 Aphasia syndromes
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34 Historically, language was the first cortical function associated with specific brain lesions, setting the
35 first precedent for topographic neurology. (13) Language represents a complex system of symbols
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and rules used for communication. Aphasia, or dysphasia, is an acquired loss or impairment of
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38 language function. The left hemisphere (usually the dominant hemisphere) participates in linguistic
39 components (phonetic, phonemic, semantic/lexical, syntactic, pragmatic) of verbal and non-verbal
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communication (reading and writing). Non-linguistic components of language as emotion,

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42 inflection, cadence, and prosody, depend on the function of both hemispheres. The cortical
43 structures involved in verbal language locate in the perisylvian area, temporal association areas,
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44 supramarginal gyrus, arcuate fasciculus, and Broca’s area. Some other subcortical structures as the
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46 caudate nucleus, putamen and thalamus influence the content of language.
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48 Wernicke’s area decodes sounds into linguistic information, while temporal association areas are
49 involved in word significance. The supramarginal gyrus, as somatosensory associative area, is
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related with phonemic processing and production. On the other hand, the Broca’s area oversees
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52 language motor programming and the arcuate fasciculus associates frontal motor with temporal
53 receptive language areas.
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1
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3 Regarding non-verbal language, the occipitotemporal, parietotemporal and anterior cortex
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participate in reading, while the Exner’s and primary motor areas participate in writing. (14)
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7 Benson and Geschwind proposed a bedside approach to patients with aphasia, used for topographic
8 diagnosis in clinical practice. They evaluated language in seven steps for the integration of classic
9 aphasia syndromes (table 2): spontaneous speech (fluence), nomination, comprehension,
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11 repetition, reading, writing and additional features.
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13 Aphasia Syndrome F N C Rep Rea W Additional features Lesion Location
14 Motor or non-fluent - - + - - - Right faciobrachial Posterior region of
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15 (Broca’s) hemiparesis and inferior frontal gyrus
16 hemihypesthesia (Brodmann’s areas
17 44 and 45)
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18 Sensitive or fluent + - - - - - Right hemianopia Posterior region of
19 (Wernicke’s) superior temporal
20 gyrus and posterior
21 inferior parietal lobe
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22 (Brodmann’s area
23 22)
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Global - - - - - - Right faciobrachial Perisylvian cortical

25 hemiparesis, structures
26 hemihypesthesia
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and hemianopia
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Conduction + + + - + + Apraxia of left limbs, Between superior
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(Associative central, mild right temporal gyrus and
or
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commissural) hemiparesis, right inferior parietal lobe
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hemihypesthesia (supramarginal gyrus
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and right and arcuate
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hemianopsia fasciculus)
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35 Anomic (amnesic, + - + + + - Gerstmann Angular gyrus,
36 nominal) syndrome associative temporal
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37 areas
38 Motor Transcortical - - + + - - Variable Supplementary
39 motor area, frontal
40 lobe white matter,
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41 adjacent areas to
42 Broca’s area.
43 Sensitive + - - + - - Variable Temporo-occipital
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44 Transcortical cortex
45 Mixed Transcortical - - - + - - Variable Long watershed
46 ischemic infarction
47 Subcortical - - - - - - Awareness Anterior part of
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48 /+ (mild) (mild) fluctuation, right putamen,

49 or + hemiplegia, paramedian and
50 dysarthria anterior thalamic
51 nucleus, head of
52 caudate nucleus,
53 anterior arm of
54 internal capsule.
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3 Table 2. Classic aphasia syndromes. F= Fluence (onset, articulation, phonation, tone, volume,
4 velocity, prosody, length of phrases, effort, paraphasias, neologisms); N= Nomination (naming
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objects, its parts, pictures, colors. Make sure that patient knows objects); C= Comprehension (motor
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commands of one, two or three steps and nonmotor commands. R= Repetition (words and phrases).
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Classically, aphasia syndromes have been described in vascular lesions (ischemic stroke). Occlusion
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11 of the middle cerebral artery can produce Broca’s, Wernicke’s, global and conduction aphasias.
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12 Motor transcortical aphasia is caused by anterior cerebral artery infarction, while mixed
13 transcortical aphasia by superficial watershed infarction in the context of carotid artery stenosis.
14 Any type of lesions located in perisylvian structures of the left hemisphere can produce any aphasia
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15 combinations of language alterations.
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19 Frontal lobe syndromes
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21 The frontal lobes comprise one third of the human cortex. They participate in motor control,
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22 language, and executive tasks. For this reason, frontal lesions present with a wide diversity of clinical
23 manifestations as weakness, aphasia, and/or important personality changes. (15) Throughout
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history, three classical frontal syndromes have been described based on frontal lobe topography:
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26 orbitofrontal syndrome, medial frontal syndrome, and dorsolateral syndrome. As a note, these
27 three syndromes comprise mainly prefrontal topographic regions. Motor and language deficits may
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28 be part of frontal syndromes but are usually described independently (see altered eye movement
29 disorder syndromes, upper motor neuron syndromes and aphasia syndromes). (16)
or
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31 Orbitofrontal prefrontal syndrome
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33 Lesions in the orbitofrontal cortex (ventral or inferior) cause this syndrome. (17) Many authors also
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34 call it “pseudosociopathy” or “acquired sociopathy”, because patients present with impulsivity,

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aggressivity, impaired judgement, inability to make decisions, a “hollow” jocularity termed
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37 Witzelsucht and lack of empathy. Moreover, it is also common to see concentration deficits and
38 difficulties achieving goals. (18) Orbitofrontal syndrome is caused by frontal tumors, infarction,
39 hemorrhage, trauma, or infection.
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41 Medial prefrontal syndrome

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43 Medial prefrontal lesions cause motivation and willful behavior abnormalities. The less severe form
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44 is called “apathy” and the main symptoms are decline in spontaneous movement, language, and
45 gesticulation. The severe form of medial prefrontal syndrome is known as “abulia”. Akinetic mutism
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presents if both medial prefrontal cortexes are involved. Some specific clinical characteristics in this
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48 syndrome are the loss of voluntary activity with spontaneous visual tracking of environmental
49 stimuli and the reduction in the word fluency tests. (19,20) Medial prefrontal syndrome is caused
50 by frontal tumors, hydrocephalus, infarction, hemorrhage, dementia, trauma, or infection.
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52 Prefrontal dorsolateral syndrome (Dysexecutive syndrome)
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54 The prefrontal cortex is a complex area involved in cognitive abilities such as attention, inhibition,
55 task planning and coding of new information. (21) Patients with prefrontal dorsolateral syndrome
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3 present with perseverant behavior, planning and task shifting difficulty, working memory
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impairment and impairment of sequential motor tasks (such as Luria’s sequence). These deficits can
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6 be elicited using different tests for verbal and nonverbal fluency, as well as using drawings with
7 alternate figures. The causes of dorsolateral syndrome are similar as in orbitofrontal syndrome.
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11 Cognitive decline syndromes
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Major cognitive decline disorders (previously known as dementia) are among the leading causes of
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14 death and disability worldwide. Due to the increasing aging population, its prevalence is expected
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15 to nearly triple by 2050. (22) Dementia is defined as cognitive and behavioral changes that can cause
16 decline from baseline function levels (leading to social and/or occupational dysfunction), requiring
17 impairment in at least two neuropsychiatric or cognitive domains that are not better explained by
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nondegenerative or primary psychiatric disorders, as well as systemic conditions such as delirium.
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20 (23) The American Psychiatric Association’s proposed in the Diagnostic and Statistical Manual fifth
21 edition (DSM-5) the following diagnostic criteria for major cognitive decline: (24)
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23 A. Evidence of significant cognitive decline from a previous level of performance in one or
24 more cognitive domains (complex attention, executive function, learning and memory,
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25 language, perceptual–motor, or social cognition) based on:

26 a. Concern of the individual, a knowledgeable informant, or the clinician that there
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28 has been a significant decline in cognitive function; and

29 b. A substantial impairment in cognitive performance, preferably documented by
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30 standardized neuropsychological testing or, in its absence, another quantified

31 clinical assessment.
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B. The cognitive deficits interfere with independence in everyday activities (that is, at a
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34 minimum, requiring assistance with complex instrumental activities of daily living such as
35 paying bills or managing medications).
36 C. The cognitive deficits do not occur exclusively in the context of a delirium.
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37 D. The cognitive deficits are not better explained by another mental disorder
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40 Rapidly progressive cognitive decline, or dementia, refers to a condition that fulfills criteria for major
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41 cognitive decline in less than 1-2 years, although most cases occur within weeks to months. Rapidly
42 progressive dementias entails a different diagnostic approach than slowly progressive
43 neurodegenerative dementias. (25) There are many causes of rapidly progressive dementia and a
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useful mnemonic for the differential evaluation is the acronym VITAMINS: vascular, infectious, toxic-
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46 metabolic, autoimmune, malignancy, iatrogenic, neurodegenerative (including prion diseases and
47 rapidly progressive presentation of Alzheimer's disease, frontotemporal dementia, subcortical
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48 ischemic vascular disease, dementia with Lewy bodies, corticobasal degeneration and progressive
49 supranuclear palsy), and systemic/seizures/structural etiologies. (26)
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51 Mild cognitive impairment (MCI) shares similar characteristics than major cognitive disorder
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criterion, except that the cognitive impairment does not interfere with capacity for independence
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54 in everyday activities (that is, complex instrumental activities of daily living such as paying bills or
55 managing medications). MCI can divide in four types: amnestic (only memory deficit), single-domain
56 nonamnestic (without memory deficit and only one cognitive domain affected such as attention,
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3 language, visuospatial, or executive function), multiple-domain amnestic (memory deficit and one
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or more altered cognitive domains); and multiple-domain nonamnestic (more than one cognitive
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6 domain compromised but preserved memory). MCI is associated with etiologies such as systemic
7 diseases, neurological diseases, medications, and psychiatric disorders. Amnestic MCI is the typical
8 prodromal stage of dementia due to Alzheimer’s disease, logopenic aphasia, posterior cortical
9 atrophy or frontal lobe-dysexecutive presentation of Alzheimer’s disease. Multi-domain amnestic
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MCI can precede Alzheimer’s disease or vascular cognitive impairment. Single-domain nonamnestic
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12 MCI can be a prodromal for fronto-temporal dementia or Alzheimer’s disease. Multi-domain
13 nonamnestic MCI can progress to dementia with Lewy bodies, Alzheimer’s disease, or vascular
14 cognitive impairment. (27)
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18 Disconnection syndromes
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20 Disconnection syndromes are a cluster of clinical syndromes produced by a disruption of pathways
21 from one brain area to another. (28) Classically, there are four disconnection syndromes: conduction
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22 aphasia, alexia without agraphia, ideomotor apraxia and visual agnosia. (29)
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24 Conduction aphasia is characterized by a repetition deficit and paraphrastic speech, with fluent
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25 verbal output and intact comprehension. The topography of the lesion is the arcuate fasciculus,
26 which connects both Wernicke’s and Broca’s areas.
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28 In alexia without agraphia, also known as “pure alexia”, written language comprehension is lost but
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writing ability is intact. It is caused by separation of both right and left hemisphere visual regions
or
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31 from the left angular gyrus. These patients often have damage to the splenium of the corpus
32 callosum but can be caused also by lesions that affect the left occipital cortex.
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34 There are three subtypes of ideomotor apraxia: callosal apraxia, sympathetic apraxia, and parietal
35 apraxia. Callosal apraxia typically presents as left limb apraxia (inability to follow commands for left
36 limb movements), agraphia, and tactile anomia. Sympathetic apraxia presents as inability of the
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37 nonpathologic hand to carry out commanded movements. Parietal apraxia presents with bilateral
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39 apraxia. In callosal and sympathetic apraxia, there is an isolation of the right hemisphere from the
40 left hemisphere. The callosal apraxia is caused by disruption of the anterior corpus callosum
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41 interhemispheric fibers and the sympathetic apraxia by disruption in the interhemispheric

42 projections. (30,31) Lesions in the left supramarginal gyrus lead to bilateral apraxia (parietal
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apraxia).
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45 Visual agnosia is the inability to recognize even commonplace objects presented visually with intact
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visual perceptual abilities and language. It is caused by disconnection of visual areas from the
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48 inferior parietal lobe, and hence indirectly to Wernicke’s area. Visual agnosia can be divided in visual
49 object ventral pathway agnosia (prosopagnosia for faces, topographagnosia for landmarks, cerebral
50 achromatopsia for colors, body form agnosia), and visual spatial dorsal pathway agnosia (cerebral
51 akinetopsia for movement, orientation agnosia for the placement of objects in space, optic ataxia,
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autotopagnosia and heterotopagnosia, agnosia for mirror stimuli).
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Moreover, Geschwind described other disconnection syndromes: pain asymbolia, verbal learning
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56 impairment, tactile anomia, pure word deafness and anosognosia. Pain asymbolia presents as
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1
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3 absent response to pain in the presence of normal tactile discriminatory function, caused by
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disconnection of somatosensory cortex from the limbic lobe. Verbal learning impairment is
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6 associated in disconnection of the auditory cortex from the limbic lobe. Tactile aphasia is defined as
7 the inability to name a held object in the presence of preserved speech and naming in other sense
8 modalities and is caused by disconnection of Wernicke’s area or the angular gyrus from somesthetic
9 areas. Pure word deafness is the inability to understand spoken words in the presence of preserved
10
hearing, secondary to disconnection of Wernicke’s area from primary auditory cortex. Anosognosia
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12 presents with lack of awareness of a neurological deficit. It occurs particularly in patients with
13 nondominant parietal lesions, although case reports have demonstrated that premotor loop, aslant
14 tract, insular and temporal pole lesions can present with anosognosia. (32,33)
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18 Cephalalgia syndrome or headache syndrome
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20 Headache is defined as pain located in the head, above the orbitomeatal line and/or nuchal ridge.
21 (34) Headache can be produced by activation of peripheral nociceptors with several kinds of
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22 stimulus in extracranial structures (skin, nasal and oral mucosa, facial and masticatory muscles,
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arteries, veins, and periosteum of cranial bones) and intracranial structures (dura mater and
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25 intracranial blood vessels), which are innervated by trigeminal and major occipital nerves that
26 transmit the nociceptive information to trigeminal nucleus caudalis and the C1 and C2 dorsal horns
27
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of the spinal cord respectively, and then to thalamus and somatosensory cortex. Headache
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29 syndrome has limited valor to make topographic diagnosis in clinical practice.
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31 According to The 3rd edition of the International Classification of Headache Disorders (ICHD-3),
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33
cephalalgia disorder or headache syndromes can be classified in three main groups: 1) primary
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34 headache disorders; 2) secondary headache disorders; and 3) painful cranial neuropathies, other
35 facial pain and other headaches. (35) Primary headache disorders are the most common reasons for
36
which patients seek neurologic consultation. (36) Distinguishing primary headache from secondary
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38 headache is the main objective of every new clinical encounter with a patient complaining of
39 headache, because may be life threatening if not diagnosed expeditiously. (37) Performing
40 laboratory and image testing to every patient with a headache is costly and increases the chance of
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false-positive results or incidental findings. (38) Even in patients with clinical suspicion of a
43 secondary etiology, sometimes imaging testing is normal.
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An excellent tool to differentiate primary to secondary headache disorders, as well as to approach
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47 differential diagnosis is the SNNOOP10 list of red and orange flags proposed by Phu et at (Table 3):
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48 (39)
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Sign or Symptom Related Secondary Headache
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52 Systemic symptoms Headache attributed to infection or nonvascular intracranial disorders,
53 including fever carcinoid or pheochromocytoma (orange flag if isolated fever)
54 Neoplasm history Neoplasms of the brain; metastasis
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1
2
3 Neurologic deficit or Headaches attributed to vascular, nonvascular intracranial disorders; brain
4 dysfunction (including abscess and other infections
5
decreased consciousness)
6
7 Onset of headache is sudden Subarachnoid hemorrhage and other headaches attributed to cranial or
8 or abrupt cervical vascular disorders
9 Older age (after 50 years) Giant cell arteritis and other headache attributed to cranial or cervical
10 vascular disorders; neoplasms and other nonvascular intracranial disorders
11
Co
Pattern change or recent Neoplasms, headaches attributed to vascular, nonvascular intracranial
12
13 onset of new headache disorders
14 Positional headache Intracranial hypertension or hypotension
nf
15 Precipitated by sneezing, Posterior fossa malformations; Chiari malformation
16 coughing, or exercise
17
ide
Papilledema Neoplasms and other nonvascular intracranial disorders; intracranial
18
19 hypertension
20 Progressive headache and Neoplasms and other nonvascular intracranial disorders
21 atypical presentations
nt
22 Pregnancy or puerperium Headaches attributed to cranial or cervical vascular disorders; postdural

23 puncture headache; hypertension-related disorders (e.g., preeclampsia);
24
ial
cerebral sinus thrombosis; hypothyroidism; anemia; diabetes denial or

25
26 cervical vascular disorders
27 Painful eye with autonomic Pathology in posterior fossa, pituitary region, or cavernous sinus; Tolosa-
:F
28 features Hunt syndrome; ophthalmic causes

29 Posttraumatic onset of Acute and chronic posttraumatic headache; subdural hematoma and other
or
30
headache headache attributed to vascular disorders
31
32 Pathology of the immune Opportunistic infections and tumors
33 system such as HIV
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34 Painkiller overuse or new Medication overuse headache; drug incompatibility

35 drug at onset of headache
36
vie
37
Table 3. SNOOP10 list of red and orange flags.
38
39
40
w
41 Seizure (Convulsive) syndrome and epilepsy

42
43 A seizure is defined as “a transient occurrence of signs and/or symptoms due to abnormal excessive
On
44 or synchronous neuronal activity in the brain.” Multiple seizure types exist and include motor and
45
nonmotor features. Motor seizures include automatisms, atonic, clonic, epileptic spasms,
46
47 hyperkinetic, myoclonic, and tonic. Nonmotor seizures include autonomic, behavior arrest,
ly
48 cognitive, emotional, sensory, typical, and atypical absences, and eyelid myoclonus. A seizure
49 syndrome is considered when a patient presents symptoms or signs that suggest a seizure (motor
50 or nonmotor).
51
52 The most recent classification of seizure types was published by the International League Against
53 Epilepsy in 2017 and the extended version goes as follows (Table 4): (40)
54
55
56
57
58
59
1
2
3 Focal onset Generalized onset Unknown onset
4
Aware Impaired Awareness Motor Motor
5
Motor onset Tonic-clonic Tonic-clonic
6
7 Automatisms Clonic Epileptic spasms
8 Atonic Tonic
9 Clonic Myoclonic Non motor
10 Epileptic spasms Myoclonic-tonic-clonic Behavior arrest
11 Myoclonic-atonic
Co
Hyperkinetic
12 Myoclonic Atonic
13 Tonic Epileptic spasms
14
nf
15
16 Non motor onset Non motor
17 Autonomic Typical
ide
18 Behavior arrest Atypical
19 Cognitive Myoclonic
20 Emotional Eyelid myoclonus
21 Sensory
nt
22 Focal to bilateral tonic-clonic Unclassified

23
24
Table 4: ILAE 2017 Classification of Seizure Types Expanded Version.
ial
25
It is important to understand that awareness means the person is aware of self and environment
26
27 during the seizure, even if immobile. Cognitive seizures imply impaired language or other cognitive
:F
28 domains or positive features such as Deja vu, hallucinations, illusions, or perceptual distortions.
29 Emotional seizures involve anxiety, fear, joy, other emotions, or appearance of affect without
or
30 subjective emotions. Correct identification of seizures helps the clinician to initiate workup, as well
31
as to define which patients fulfill the diagnosis of epilepsy and guide further treatment. Epilepsy is
32
33 a disease characterized by an enduring predisposition to generate epileptic seizures and by the
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34 neurobiological, cognitive, psychological, and social consequences of this condition.

35
36 The ILAE defines epilepsy as any of the following:
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37
38  At least two unprovoked (or reflex) seizures occurring greater than 24 hours apart.
39  One unprovoked (or reflex) seizure and a probability of further seizures similar to the
40 general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the
w
41 next 10 years.
42
43  Diagnosis of an epilepsy syndrome
On
44
45
46 Afferent visual disorder syndrome
47
ly
48 The visual pathway includes the retina, optic nerves, optic chiasma, optic tracts, lateral geniculate
49
nuclei, optic radiations, and visual cortex. For localization purposes, visual abnormalities can be
50
51 divided clinically into prechiasmal, chiasmal and postchiasmal disorders. Additionally, postchiasmal
52 may be subdivided into pregeniculate and postgeniculate disorders. Visual disorders have a high
53 yield for anatomic localization.
54
55 Retrobulbar prechiasmal disorders present monocular symptoms and signs as the distinctive
56 feature. Patients complain of diminished visual acuity or complete visual loss, as well as altered color
57
58
59
1
2
3 vision and contrast. Other presentations include a monocular altitudinal defect, central scotoma, or
4
far temporal field decrease. (41) In examination, patients present with afferent pupillary defect or
5
6 loss of ipsilateral photomotor and contralateral consensual responses. These presentations must
7 orient the clinician to a prechiasmal localization. Common etiologies of prechiasmal disease include
8 optic neuritis (mostly secondary to multiple sclerosis and anti-MOG), optic neuropathies (ischemic,
9 metabolic, toxic, infectious), trauma, tumors, or infiltrative disorders. Trauma, tumors, or infiltrative
10
disorders usually present with other cranial nerves involvement (see multiple cranial neuropathy
11
Co
12 syndromes). (42,43)
13
14
Chiasmal disorders present with bitemporal hemianopia. These patients have little or no complaint
nf
15 in visual acuity or color vision. Other manifestations are postfixation blindness, or photophobia in
16 acute chiasmatic syndromes. The most common etiologies are pituitary tumors, particularly
17 adenomas. Other causes may include meningiomas, gliomas, craniopharyngioma,
ide
18 neurofibromatosis, internal carotid aneurysms, pituitary apoplexy, and optic neuritis secondary to
19
20
neuromyelitis optica (typically affects both prechiasmal and chiasmal portions of the optic nerve).
21 (44)
nt
22
23 Features of pregeniculate diseases include contralateral homonymous hemianopias that can be
24 complete or incomplete. The difference between pregeniculate and postgeniculate disorders is
ial
25 incongruity, defined as differences in the visual field perception between the eyes. The closer the
26 lesion to the visual cortex, the more congruous it will be. Thus, patients with pregeniculate lesions
27
:F
perceive hemianopia predominantly in one eye compared with the other. Congruity is difficult to
28
29 identify with clinical confrontation, so we suggest visual fields as the method of choice. Causes
include infarction, hemorrhage, tumors, abscesses, or demyelinating disorders. (45)
or
30
31
32 Postgeniculate disorders present with contralateral homonymous hemianopia or quadrantanopia.
33 Temporal lobe lesions cause contralateral superior homonymous visual field loss, and parietal lobe
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34 lesions cause contralateral inferior homonymous visual field loss. Temporal and parietal lesions are
35 usually incongruous, while occipital lobe lesions are congruous. In case both occipital lobes are
36
affected, patients often do not recognize their deficit and confabulate. This is known as Anton
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37
38 syndrome. (46) Causes of postgeniculate disorders include infarction, hemorrhage, tumors,
39 demyelinating disease, or posterior reversible encephalopathy syndrome.
40
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41
42
43 Altered ocular movements syndrome
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44
45 Ocular movements have a high localization yield in neurologic examination. Abnormalities are
46 classified into four categories: supranuclear, internuclear, nuclear and infranuclear.
47
ly
48 Supranuclear and internuclear ocular motor disorders are caused by damage in structures of the
49 encephalon before eye movement signals reach the ocular motor nuclei. This damage may include
50 lesions in the brainstem (medulla, pons, and midbrain), cerebellum, and cerebrum (thalamus, basal
51 ganglia, and cerebral hemispheres). (47) The main etiologies are infarction, tumors, infections,
52
53
demyelinating disorders, and neurodegenerative disorders. Supranuclear disorders do not cause
54 disconjugate palsies as internuclear, nuclear and infranuclear disorders. (48)
55
56 Locations that cause supranuclear ocular movements abnormalities include the following: (49)
57
58
59
1
2
3 ● Frontal eye field lesion: presents acutely with ipsilesional gaze deviation, and chronically
4
with increased latency of predictive and memory-guided saccades, with impaired smooth
5
6 pursuit and optokinetic nistagmus towards the side of the lesion.
7 ● Primary visual cortex lesion: presents with impaired saccades and smooth pursuit in blind
8 hemifield.
9 ● Parietal lobe lesion: presents with ipsilesional gaze deviation, contralesional inattention
10
(non-dominant hemisphere), increased latency of saccades and impaired smooth pursuit.
11
Co
12 ● Caudate nucleus lesion: presents with hypometric contralateral memory-guided saccades
13 with increased latency.
14 ● Middle temporal visual area: presents with scotoma of motion in contralateral hemifield.
nf
15 ● Dorsal vermis lesions: present with hypometric ipsilesional saccades, hypermetric
16
contralesional saccades and impaired smooth pursuit toward the side of lesion. Causes will
17
ide
18 be discussed in cerebellar syndromes (see cerebellar syndromes).
19 ● Fastigial nucleus lesions: present with hypermetric ipsilesional saccades and impaired
20 contralateral smooth pursuit. It may cause opsoclonus. Causes will be discussed in
21 cerebellar syndromes.
nt
22
23 Locations that cause internuclear ocular movements abnormalities include the following: (50)
24
ial
25 ● Paramedian pontine reticular formation: clinical findings include ipsilateral saccadic palsy,
26 with or without ipsilesional smooth pursuit and vestibulo-ocular reflexes. It may be caused
27
:F
by demyelinating disorders, infarction, trauma, hemorrhage, or infections.

28
29 ● Medial longitudinal fasciculus: presents with ipsilateral internuclear ophtalmoplegia
(ipsilesional adducing deficit, abducting nystagmus of contralateral eye, skew deviation and
or
30
31 dissociated vertical nystagmus). It may be caused by multiple sclerosis, infarction,
32 hydrocephalus, trauma, infectious or neoplastic disorders. (51)
33
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● Combined abducens nucleus, medial longitudinal fasciculus and paramedian pontine

34
35 reticular formation: ipsilateral one and-a-half syndrome (ipsilateral conjugate gaze palsy
36 plus adducing deficit of contralateral eye). It is caused by demyelinating disorders,
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37 infarction, tumor, hemorrhage, or trauma. (52)

38 ● Interstitial nucleus of Cajal: presents with impaired vertical gaze holding, skew deviation
39
40
and torsional nystagmus with ipsilesional quick phases.
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41
Nuclear and infranuclear ocular motor disorders are caused by lesions in the oculomotor, trochlear,
42
43 or abducens nerves that may be located anywhere from the ocular motor nuclei to the termination
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44 of the nerves in the extraocular muscles. These disorders are common causes of binocular diplopia
45 and characteristically cause disconjugate palsies. Nuclear and infranuclear disorders differ from
46 supranuclear and internuclear disorders in their clinical findings; where nuclear and infranuclear
47
ly
present with weakness of the muscles innervated by its corresponding nerve. (53)
48
49 Unilateral nuclear oculomotor (III) disorders present with contralateral superior rectus weakness
50
51
and ipsilateral medial rectus, inferior rectus, and inferior oblique weakness, with palpebral elevator
52 preservation. Peripheral oculomotor injuries present with ipsilateral ptosis and ipsilateral medial
53 rectus, superior rectus, inferior rectus, and inferior oblique weakness, including most cases pupil
54 dilation with no response to light stimuli. (54) Typically, oculomotor nuclear disorders present with
55 another midbrain symptom or sign. Principal causes include midbrain tumors, infarction, or
56
57
58
59
1
2
3 demyelinating disorders. Isolated oculomotor nerve disorders are caused by posterior
4
communicating artery aneurysms, trauma, metabolic disorders, or herniation syndromes. They can
5
6 also be part of multiple cranial neuropathies syndromes (see multiple cranial neuropathy
7 syndrome). (55)
8
9 Trochlear (IV) nuclei injury causes contralateral superior oblique weakness. After its exit through the
10 quadrigeminal cistern, any disorder will present as ipsilateral superior oblique weakness. Clinical
11 diagnosis may be performed with Parks-Bielchowsky algorithm. Causes of isolated nuclear trochlear
Co
12 affection includes trauma, tumor, or demyelinating disorder. It may also be part of a midbrain
13
14
syndrome. Isolated peripheral trochlear nerve weakness may be caused by trauma or intracranial
nf
15 aneurysms. In their peripheral pathway, it is usually part of a multiple cranial neuropathy syndrome
16 (see multiple cranial neuropathy syndrome). (56)
17
ide
18 Abducens (VI) nuclei injury presents with ipsilateral lateral rectus weakness and internuclear
19 ophthalmoplegia. After exiting the brainstem, any disorder will present also ipsilateral rectus
20 weakness. Causes of isolated nuclear abducens injury include tumor, demyelinating disorder,
21
nt
hemorrhage, or infarction. It usually is part of a pons syndrome. Peripheral abducens lesions may
22
23 be caused by increased intracranial pressure, clivus tumor or mastoiditis. It is usually part also of
24 multiple cranial neuropathy syndrome (see multiple cranial neuropathy syndrome). (57)
ial
25
26
27
:F
28 Brainstem syndromes
29
The brainstem is the part of the encephalon that contains most of the ascending and descending
or
30
31 tracts, as well as cerebellar connections and cranial nerves, including nuclei and pathways. The
32 brainstem is divided into three structures: midbrain, pons, and medulla oblongata. These structures
33 are compacted in the brainstem, so a small lesion may cause important deficits including cranial
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34 nerves and ascending and descending tracts. Brainstem syndromes have a high topographic value.
35
(58) However, brainstem syndromes have a great variability of clinical presentations, turning them
36
vie
37 into a diagnostic challenge for neurologists. For this reason, we consider naming brainstem
38 syndromes by topographic nomenclature rather than by eponym.
39
40 Midbrain syndromes
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41
42 The midbrain contains the nuclei and fascicular tract of the oculomotor nerves (III) and the trochlear
43 nerves (IV), as well as the corticospinal and corticonuclear tracts contained in the cerebral
On
44 peduncles, the red nucleus, and the superior cerebellar peduncles. (59)
45
46 The clinical manifestations of midbrain syndromes include contralateral hemiplegia, contralateral
47 facial palsy, ipsilateral oculomotor palsy, contralateral tremor, and contralateral ataxia. An
ly
48 ipsilateral oculomotor palsy and contralateral hemiparesis/plejia is known as Weber syndrome and
49
50 localizes to the midbrain base. Benedikt’s syndrome includes ipsilateral oculomotor palsy,
51 contralateral hemiparesis, contralateral tremor, and contralateral ataxia, and localizes to the
52 midbrain tegmentum. Claude’s syndrome presents with ipsilateral oculomotor palsy, contralateral
53 tremor and contralateral ataxia and localizes to the midbrain tegmentum, without compromising
54
the base. Nothnagel’s syndrome presents with oculomotor palsy (unilateral or bilateral) and
55
56 contralateral ataxia, localizing in the midbrain tectum. These syndromes are usually secondary to
57
58
59
1
2
3 infarction, although tumors, demyelinating lesions or infections may be considered in the
4
differential diagnosis.
5
6 Another midbrain syndrome is Parinaud’s, which presents with impaired upgaze, convergence
7
retraction nystagmus, Collier sign and dilated pupils with light-near dissociation. It is considered as
8
9 unique as it localizes to the midbrain dorsum and is mainly caused by tumors in the posterior third
10 ventricle (mainly pinealoma). (60)
11
Co
12 Medial inferior pontine syndrome (Foville syndrome)
13
14 The medial inferior region of the pons contains the abducens nerve nuclei (VI) and fascicle, the
nf
15 corticospinal tract, the paramedian pontine reticular formation, the medial lemniscus and the
16 middle cerebellar peduncle. Patients with medial inferior pontine syndrome present with ipsilateral
17 sixth nerve palsy, horizontal conjugate gaze palsy, contralateral hemiparesis, contralateral
ide
18
proprioceptive loss and ipsilateral ataxia. It is mostly associated with infarction due to occlusion of
19
20 paramedian perforating vessels. (61)
21
nt
22
Lateral inferior pontine syndrome
23
The lateral inferior region of the pons contains the facial nerve nuclei (VII) and fascicle, corticospinal
24
ial
25 tract, principal, and spinal nucleus of the trigeminal nerve (V), lateral spinothalamic tract, solitary
26 tract, middle cerebellar peduncle and flocculus. Thus, the clinical presentation of lateral inferior
27 pontine syndrome includes ipsilateral peripheral facial palsy, contralateral hemiparesis, ipsilateral
:F
28 loss of pain and temperature in the face, contralateral loss of pain and temperature of the body,
29
ipsilateral ataxia and Horner’s syndrome. This syndrome is associated with occlusion of the anterior
or
30
31 inferior cerebellar artery. (62)
32
33
Medial midpontine syndrome
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34
The medial midpontine region contains the corticospinal tract, the medial lemniscus and the middle
35
36 cerebellar peduncle. The clinical presentation includes contralateral hemiparesis, contralateral
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37 proprioceptive loss and ipsilateral ataxia. It is caused mainly by infarction secondary to occlusion of
38 paramedian arteries.
39
40 Lateral midpontine syndrome
w
41
42 The lateral midpontine region contains the principal nuclei of the trigeminal nerve (V) and the motor
43 nuclei, as well as the middle cerebellar peduncle. Clinical presentation includes weakness of the
On
44 ipsilateral masticatory muscles, ipsilateral sensory loss in the face and ipsilateral ataxia. It is
45
associated with short circumferential artery occlusion.
46
47
ly
Medial superior pontine

48
49 The medial superior region of the pons contains the medial longitudinal fasciculus, the central
50 tegmental tract, the corticospinal tract, medial lemniscus and the middle cerebellar peduncle. It
51
52 presents with internuclear ophthalmoplegia, contralateral hemiparesis, contralateral
53 proprioceptive loss, ipsilateral ataxia and may present palatal myoclonus. It is associated with
54 paramedian perforating artery occlusion.
55
56
57
58
59
1
2
3 Lateral superior pontine
4
5 The lateral superior region of the pons contains the lateral spinothalamic tract, the medial
6 lemniscus, the middle cerebellar peduncle and the superior cerebellar hemisphere. It presents with
7
contralateral loss of pain, temperature and proprioceptive sensation, ipsilateral ataxia and skew
8
9 deviation. It is generally secondary to superior cerebellar artery occlusion.
10
11 Medial medullary syndrome (Dejerine syndrome)
Co
12
The medial region of the medulla oblongata contains the hyoglossus nuclei (XII) and fascicle, as well
13
14 as the pyramid decussation and the medial lemniscus decussation. The medial medullary syndrome
nf
15 presents with ipsilateral tongue weakness with the tongue deviating to the weak side, contralateral
16 hemiparesis (if lesion superior to decussation), contralateral proprioceptive loss (if lesion superior
17 to decussation). There are cases where the lesion can affect below the pyramid and lemniscal
ide
18
decussation, thus causing ipsilateral weakness and ipsilateral proprioceptive loss. The main cause is
19
20 anterior spinal artery occlusion.
21
nt
22
Lateral medullary syndrome (Wallenberg syndrome)
23
Lateral medullary syndrome, also known as Wallenberg syndrome, is one of the classical brainstem
24
ial
25 syndromes. The lateral region of the medulla oblongata is complex, as it contains many important
26 nuclei and tracts. The main structures contained are the vestibular nuclei, the descending
27 sympathetic fibers, the nucleus ambiguous, the solitary tract, the spinal nucleus of the trigeminal
:F
28 nerve (V), spinothalamic tract, and inferior cerebellar peduncle. The classical lateral medullary
29
syndrome presents with vertigo, nystagmus, ipsilateral Horner syndrome, decreased gag reflex,
or
30
31 weakness of ipsilateral soft palate with contralateral uvula deviation, ipsilateral decreased pain and
32 temperature sensation of the face, contralateral loss of pain and temperature sensation of the body
33 and ipsilateral ataxia. The main etiology is occlusion of the posterior inferior cerebellar artery,
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34 although there are some cases related with the vertebral artery.
35
36
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37
38 Multiple cranial neuropathy syndromes
39
40 Dysfunction of the cranial nerves can occur anywhere in their course from intrinsic brainstem
w
41 dysfunction to their peripheral courses. The term multiple cranial neuropathies include
42 extramedullary causes that affect two or more cranial nerves. (63) Thus, the clinical manifestations
43
On
44
must be infranuclear to be considered in this syndrome. The intramedullary syndromes that affect
45 multiple cranial nerves are considered within brainstem syndromes and usually affect other long
46 tracts such as corticospinal, spinothalamic, or posterior columns. Those are reviewed in Brainstem
47 syndromes.
ly
48
49 The most common combinations of affected cranial nerves are III and IV, V and VI, and V and VII.
50 (64) The principal causes in non-sequential or contiguous nerves are Guillain-Barré and its Miller-
51
Fisher variant, followed by metabolic diseases as diabetes mellitus. In GBS, facial nerve is the
52
53 commonest to be involved followed by extra ocular muscles and lower cranial nerve involvement.
54 (65) There are specific syndromes in different points in the extracranial pathways of cranial nerves:
55
56
57
58
59
1
2
3 superior orbital fissure syndrome, cavernous sinus syndrome, orbital apex syndrome,
4
cerebellopontine angle syndrome, petrous apex syndrome and Garcin’s syndrome.
5
6 Superior orbital fissure syndrome
7
8 The superior orbital fissure (SOF) is a foramen in the skull base that lies between the greater and
9 lesser wings of the sphenoid bone. It serves as a passage for both the superior and inferior divisions
10
11 of the oculomotor nerve (III), trochlear nerve (IV), ophthalmic branch of trigeminal nerve (V1),
Co
12 abducens nerve (VI) and the superior ophthalmic vein. (66)
13
14 Superior orbital fissure syndrome is characterized by ophtalmoplegia (including ptosis), proptosis,
nf
15 sensory disturbance in the distribution of the first branch of the trigeminal nerve and retroorbital
16 pain. (67)
17
ide
18 This syndrome has a high topographic value. The most common cause is trauma, followed by
19 neoplastic lesions. Other causes include inflammation, Tolosa-Hunt syndrome, infiltrative diseases,
20 and infections. (68)
21
nt
22 Cavernous sinus syndrome

23
24 The cavernous sinus is a network of veins that is part of the dural sinuses of the encephalon. Apart
ial
25 from the blood that is contained in the sinus, it serves as a passage to several vascular and nervous
26
structures, such as the internal carotid with the pericarotid plexus, oculomotor nerve (III), trochlear
27
:F
28 nerve (IV), ophthalmic and maxillary branches of the trigeminal nerve (V1, V2) and the abducens
29 nerve (VI).
or
30
31 Cavernous sinus syndrome (CSS) is characterized by ipsilateral ophthalmoplegia (including ptosis),
32 proptosis, diminished ipsilateral sensation in V1 and V2 territories in the face and ipsilateral Horner
33 syndrome (miosis, ptosis, anhidrosis and enophthalmos). Pain is reported in 35% of patients with
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34
cavernous sinus syndrome. (69)
35
36 This syndrome has a high topographic value. The most common cause is a neoplastic lesion. Other
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37
causes of CSS include: thrombophlebitis, aspergillosis, Tolosa-Hunt syndrome, inflammatory
38
39 pseudotumor, aneurysm of the internal carotid artery, carotid–cavernous fistula and dural
40 arteriovenous shunt. (70)
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41
42 Orbital apex syndrome
43
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44 The orbital apex is formed by the superior orbital fissure and the optical canal. It includes the
45 structures that pass through the superior orbital fissure discussed earlier: the superior and inferior
46 divisions of the oculomotor nerve (III), trochlear nerve (IV), ophthalmic branch of trigeminal nerve
47
ly
(V1), abducens nerve (VI) and the superior ophthalmic vein; and the ones that pass through the
48
optic canal: optic nerve (II) and ophthalmic artery. (71)
49
50 Orbital apex syndrome presents with ipsilateral ophthalmoplegia (including ptosis), diminished
51
52 visual acuity/blindness, proptosis, and Horner syndrome. (72)
53
As SOF and CSS, the orbital apex syndrome has a high topographic value. Causes include neoplastic
54
55 lesions, trauma/iatrogenic, trauma, infectious disorders, inflammatory (sarcoidosis, Tolosa-Hunt,
56 IgG-4) and thyroid ophthalmopathy. (73)
57
58
59
1
2
3 Pontocerebellar angle syndrome
4
5 The cerebellopontine angle (CPA) is a triangular space located posterior to the pyramid, inferior to
6 the tentorium, lateral to the pons, and ventral to the cerebellum. It contains the trigeminal nerve
7
(V), facial nerve (VII), vestibulocochlear (nerve) and part of the cerebellar hemisphere.
8
9 It presents clinically with ipsilateral facial sensory loss, ipsilateral facial palsy, hearing loss, tinnitus,
10
11 and ipsilateral ataxia. (74)
Co
12
As with most multiple cranial neuropathies, it has a high localizing value. The principal etiology is
13
14 vestibular Schwannoma, followed by other tumors, metastasis, vascular disorders, and infiltrative
nf
15 diseases. (75)
16
17 Petrous apex syndrome (Gradenigo syndrome)
ide
18
19 The petrous apex is a pyramid-like structure in the petrous base of the temporal bone. The
20 trigeminal nerve (V) and abducens nerve (VI) pass through the petrous apex. Clinically manifests
21 with ipsilateral facial pain and sixth nerve palsy. It has a high topographic value. The most common
nt
22 cause are mastoid infections, followed by petrous apex tumors. (77)

23
24 Garcin’s syndrome
ial
25
26 Garcin’s syndrome consists in ipsilateral progressive unilateral compromise of cranial nerves III-XII.
27
:F
It was first described in 1927. It presents clinically with unilateral paralysis of all or most of the
28 cranial nerves from III to XII. Usually the cranial nerves affected are unilateral, but there are few
29
cases that can present bilaterally. The underlying cause is usually a sarcoma or carcinoma of the
or
30
31 skull base. The pathogenesis of Garcin's syndrome is mainly determined by the slow localized
32 growth of these tumors, rather than by their histology and primary localization. (77)
33
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34 Jugular foramen syndromes and lower cranial nerves syndromes

35
36 The jugular foramen is one of a pair of openings between the lateral occipital bone and the petrous
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37 segment of the temporal bone. Each foramen serves as a conduct for glossopharyngeal, vagus, and
38 accessory spinal nerves (cranial nerves IX, X and XI, respectively), the petrosal sinus, sigmoid sinus,
39 some meningeal branches from ascending pharyngeal and occipital arteries. Hypoglossal nerve
40
w
41 (cranial nerve XII) passes through the analogous canal just above the occipital condyle, while the
42 internal carotid artery with the sympathetic plexus enters the carotid canal near the jugular
43 foramen. (78, 79)
On
44
45 The lower cranial nerves can be affected in different combinations inside or outside of the jugular
46 foramen by several neoplastic and infectious processes, direct and indirect injury by trauma or local
47
ly
surgery and fractures of the skull base (Table 5). (80-81)

48
49 Syndrome Clinical features Affected Etiologies
50 structures
51 Jugular foramen Ipsilateral paresis of the palate, Cranial nerves IX, Glomus jugular tumors, basal
52 syndrome vocal cords (dysphonia), X and XI skull fractures, neuroma,
53 (Vernet) sternocleidomastoid, trapezius; metastasis to the skull base,
54 dysphagia; loss of taste in cholesteatoma, meningioma,
55 posterior third of tongue, giant cell arteritis.
56
57
58
59
1
2
3 anesthesia of palate, pharynx,
4 and larynx.
5 Collet-Sicard As previous more palsy and Cranial nerves IX, Condylar and Jefferson’s
6 atrophy of ipsilateral half of X, XI and XII fractures, internal carotid
7 tongue artery dissection, Lyme
8 disease, primary and
9 metastatic tumors,
10 fibromuscular dysplasia of
11
Co
carotid artery, meningitis,
12 carcinomatous meningitis.
13
Posterior As previous more ipsilateral Cranial nerves IX, Nasopharyngeal carcinoma,
14
retropharyngeal Horner syndrome X, XI and XII; abscesses, adenopathies,
nf
15
(Villaret) sympathetic aneurysm of carotid artery,
16
carotid plexus birth injury, carotid
17
ide
endarterectomy
18
Matador’s Paralysis of vocal cords, Cranial nerves X Metastases, carotid and
19
disease (Tapia) dysphagia, anesthesia of pharynx and XII, and or vertebral artery dissections.
20
21 and larynx; with or without weak cranial nerve XI
nt
22 trapezius and and sympathetic

23 sternocleidomastoid and Horner carotid plexus
24 syndrome
ial
25 Jackson Ipsilateral paralysis of the palate, Cranial nerves X, Tumors, trauma, aneurysms,
26 larynx, sternocleidomastoid, XI and XII iatrogenic
27 trapezius and tongue.
:F
28 Schmidt (Vago- Ipsilateral paralysis of vocal cord, Cranial Nerves X Primary skull base tumors;
29 spinal) sternocleidomastoid, soft palate, and XI metastases from prostate,
larynx and trapezius. breast, and cervix; skull
or
30
31 fractures; internal carotid
32 artery dissection; internal
33 jugular vein thrombosis
Re
34 Rowland Payne Palsy of the recurrent laryngeal Cranial nerve X, , Breast cancer extending
35 nerve; phrenic and vagal nerves; phrenic nerve, behind the carotid sheath at
36 preganglionic Horner syndrome preganglionic the C6 level.
vie
37 sympathetic
38 fibers
39 Table 5. Jugular foramen and lower cranial nerves syndromes.
40
w
41
42
43 Hyperkinetic syndromes
On
44
45 The hyperkinetic disorders are a heterogeneous group of diseases characterized by excessive
46 involuntary movement. These are associated with abnormally low basal ganglia output from the
47 internal segment of globus pallidus and substantia nigra pars reticulata (overactivity of direct
ly
48 pathway), causing tendency spontaneous discharges of the thalamocortical neurons. (82) There are
49
50 many types of hyperkinetic syndromes:
51
Dystonia: is a movement disorder characterized by sustained or intermittent muscle contractions
52
53 causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are
54 typically patterned, twisting, and may be tremulous. Dystonia is often initiated or worsened by
55 voluntary action and associated with overflow muscle activation. (83) The dystonic movement are
56
57
58
59
1
2
3 not too fast and not too slow, not too rhythmic, and not too big and not too small; and can be
4
accompanied by ancillary features such as sensory tricks, task specificity, null point, state function,
5
6 mirror dystonia and co-contraction. (84)
7
Tremor: is an involuntary, rhythmic, oscillatory movement of a body part. Clinically, It is divided in
8
9 action tremor and rest tremor (tremor in a body part that is not voluntarily activated). Action tremor
10 occurs while voluntarily maintaining a position against gravity (postural tremor and orthostatic
11 tremor) or during any voluntary movement (kinetic tremor). Kinetic tremor is subdivided into simple
Co
12 kinetic tremor (is roughly the same throughout a movement) and intention tremor (a crescendo
13
14
increase in tremor occurs as the affected body part approaches its visual target). Other forms of
nf
15 action tremor are position-specific postural tremor, when maintaining a specific position or posture,
16 and task-specific kinetic tremor, which occurs during a specific task such as writing. Isometric tremor
17 occurs during a muscle contraction against a rigid stationary object, as when making a fist or
ide
18 squeezing an examiner’s fingers. (85)
19
20 Chorea: it is characterized by random and flowing quality of the movements, giving it a dancelike
21
nt
appearance. (86)
22
23 Athetosis: it is considered as a variant of chorea or of dystonia. Its characteristics are slow writhing
24
ial
movements typically involving distal extremities, although other body parts can be involved.
25
26 Ballism: is a variant of chorea characterized by large amplitude finding movements involving
27
:F
28 proximal extremities.
29
Myoclonus: is a sudden, brief, lightninglike muscle contraction. It may occur from an increase in
or
30
31 contraction activity (positive myoclonus) or inhibition of contraction activity (negative myoclonus).
32 (87) There are many forms of myoclonus classification. Physiologic classification divides them in
33 cortical, subcortical/non segmental, segmental, and peripheral myoclonus using electrophysiologic
Re
34 tests. Also, myoclonus may be classified in physiologic, essential, epileptic, and symptomatic,
35
depending on etiology based by characteristic of the presentation of each syndrome.
36
vie
37 Tics: are defined as sudden, rapid, recurrent, nonrhythmic motor movements or vocalizations
38
39 (phonic productions). Tics are classified into two larger categories (motor and phonic), with each
40 being subdivided into a simple and complex grouping. Simple motor tics are movements that involve
w
41 only a single muscle or localized muscles group while complex motor tics involve either a cluster of
42 simple actions or a more coordinated pattern of movements. Characteristics of simple phonic tics
43
On
are various types of sounds or noises (grunts, barks, hoots, hollers, moans, groans, sniffs, and throat
44
45 clearing). Complex phonic tics involve linguistically meaningful vocalizations and utterances; the
46 repetition of words, syllables, or phrases; echolalia or coprolalia. (88)
47
ly
48
49
50 Parkinsonism syndrome
51
Parkinsonism is defined by the Movements disorders Society (MDS) as bradykinesia, in combination
52
53 with either rest tremor, rigidity, or both. (89) These features must be clearly demonstrable and not
54 attributable to confounding factors. Parkinsonism is the cardinal feature not only for Parkinson’s
55
56
57
58
59
1
2
3 disease, but also for atypical parkinsonisms as multiple system atrophy, progressive supranuclear
4
palsy and corticobasal degeneration. (90)
5
6 Red flags in parkinsonism that point to other diagnosis than Parkinson’s disease are: (91)
7
8 ● Rapid progression of gait impairment requiring the use of a wheelchair in less than 5 years.
9 ● Absence of progression of symptoms in 5 years without treatment
10
11 ● Early bulbar dysfunction (dysphonia, dysarthria, and dysphagia) within the first five years of
Co
12 the disease.
13 ● Inspiratory respiratory dysfunction (stridor or sighs)
14 ● Severe autonomic failure in the first five years of the disease (orthostatic hypertension and
nf
15
severe urinary incontinence)
16
17 ● Recurrent falls because of impaired balance within the first 3 years.
ide
18 ● The presence of disproportionate anterocollis or contractures of hand and feet within the
19 first 10 years.
20 ● Absence of sleep dysfunction, autonomic dysfunction, hyposmia or psychiatric symptoms
21
nt
● Unexplained pyramidal tract signs (excluding hyperreflexia)
22
23 ● Bilateral symmetric parkinsonism throughout evolution
24
ial
Parkinsonism can be localized in the basal ganglia, more specifically in the nigrostriatal pathway.
25
26 Classifying a patient with parkinsonism syndrome can be helpful to guide workup in patients with
27 red flags or in patients with another clinical syndrome, such as parkinsonism-dystonia,
:F
28 parkinsonism-ALS and parkinsonism-FTD. (92)

29
or
30
31
32 Ataxic Syndrome
33 Ataxia means “absence of order” and is a complex and heterogeneous clinical syndrome
Re
34
characterized by gait imbalance, blurry vision, slurred or scanning speech, loss of hand dexterity and
35
36 difficulty performing fine movements. (93-95) The three forms of ataxia are: cerebellar, sensory and
vie
37 vestibular. Cerebellar ataxia is the most common. (96)

38
39 Cerebellar ataxias can be classified according to etiology in three major groups: acquired ataxias,
40
w
41 hereditary ataxias, and non-hereditary degenerative ataxias. Classic clinical manifestations

42 described in the cerebellar pathology are dysmetria, asynergia or dyssynergy, a- or
43 dysdiadochokinesia, intention tremor, speech disturbances, abnormalities of posture and gait, and
On
44
hypotonia. However, there are additional motor, sensory, and cognitive symptoms and signs which
45
46 depend on the topography (See Cerebellar syndrome). (97)
47
ly
48 Sensory ataxia can be produced by pathology in the proprioceptive system along its pathway from
49 the peripheral sensory nerves, dorsal root ganglia, sensory nerve roots, dorsal column of spinal cord,
50
51 medial lemniscus of the brainstem and parietal cortices, and clinicians should have skill for localize
52 the level of lesion integrating them with other clinical manifestations. (98) Chhetri et al advised to
53 consider sensory ataxia in any patient with ataxia who has no nystagmus or cerebellar dysarthria,
54
and proposed next criteria for diagnosing clinically probable sensory ataxia: (99)
55
56
57
58
59
1
2
3 I. Ataxia confirmed by clinical examination: finger-nose incoordination and/or heel-toe ataxia
4
and/or broad-based ataxic gait.
5
6 II. Two or more of:
7 A. Romberg’s sign or ataxia significantly worse with eyes closed, or history of “wash
8 basin sign”
9
10 B. Pseudoathetosis and/or impaired joint position and/or vibration sense/s
11 C. Absence of nystagmus and/or cerebellar dysarthria.
Co
12
13
Other clinical manifestations of sensory ataxia are hypo- or areflexia, loss of pressure sensation,
14
nf
15 kinesthetic sense, and deep pain sense. The potential causes of sensory ataxia can be divided
16 according to level of lesion, if are disorder hereditary or acquired, and based on its temporal
17
ide
evolution. (100-103) (table 6). In some hereditary disorders is difficult to determine which
18
19 component a specific ataxia because usually have disfunction in the three systems (spinocerebellar
20 ataxias, autosomal recessive cerebellar ataxias, mitochondrial disorders, Fragile X-associated
21 tremor/ataxia syndrome, and other). (104)
nt
22
23
Topography Temporality Etiology Ancillary tests
24
ial
25 Peripheral Acute -Miller Fisher syndrome -Anti-GQ1b antibodies, CSF, NCS

26 nerve/nerve root -Sensory variant of GBS -Anti-ganglioside antibodies, CSF, NCS
27 -Semisynthetic penicillin
:F
-History of exposure
28
Subacute -Lyme disease -History of exposure, Lyme serology
29
-Neurosarcoidosis -CSF, NCS, ACE, Chest X ray, HP
or
30
31 Chronic -CIDP -NCS, CSF
32 -Paraproteinemia -Electrophoresis, anti-MAG
33 -Diabetes mellitus -Plasma glucose
Re
34 -Celiac disease -Anti-tTG antibodies

35 -Vitamin E deficiency -Serum vitamin E level
36
vie
37 Dorsal root Acute/Subacute -HIV, HTLV-1, HCV -Serology

38 ganglion -Paraneoplastic -Anti-Hu, CRMP-5, relevant imaging
39 neuronopathy -History of exposure; pyridoxine levels
40 -Pyridoxine intoxication -History of exposure
w
41 -Chemotherapeutic -History of exposure

42 agents* -History of exposure
43 -Thalidomide
On
44 -Organophosphate
45 exposure
46 Chronic -Sjogren’s syndrome -ENA (Anti-SSA/SSB) antibodies, lip biopsy
47
ly
-Chronic active hepatitis -RF, ANA, ASMA, hepatitis serology

48
Spinal root Chronic -CISP -NCS, SSEP, CSF, MRI
49
50 Dorsal column Acute -Posterior spinal artery -Neuroimaging
51 syndrome
52 -Hemorrhage -Neuroimaging, coagulation tests
53 -Heroin-induced -History of exposure, neuroimaging
54 myelopathy
55
56
57
58
59
1
2
3 Chronic -Vitamin B12 deficiency -Serum B12, homocysteine and methylmalonic
4 acid levels.
5 -Copper deficiency -Serum and urinary copper, serum
6 ceruloplasmin, zinc levels, hematological tests.
7 -Tabes dorsalis -Syphilis serology
8 -HIV, HCV -Serology
9 -Cervical myelopathy -Neuroimaging of spinal cord
10
-Vitamin E deficiency -Serum vitamin E, ratio of vitamin E to serum
11
Co
cholesterol and triglycerides.
12
-Myelopathy induced-N2O -History of exposure
13
14 -Sarcoidosis-associated -Neuroimaging, , CSF, ACE, Chest X ray, HP
nf
15 myelopathy
16
17
ide
Parietal Cortex Acute -Central post-stroke ataxia -Neuroimaging
18
19 Table 6. Acquired causes of sensory ataxia *Chemotherapeutic associated-myelopathy: cisplatin,
20
21 cladribine, doxorubicin, vincristine, cytosine arabinoside, intrathecal methotrexate Abbreviations:
nt
22 ACE: angiotensin-converting enzyme; ANA: antinuclear antibodies; ASMA: anti-smooth muscle

23 antibodies; CIDP: chronic inflammatory demyelinating polyradiculoneuropathy; CISP: chronic
24
ial
25
inflammatory sensory polyneuropathy; CSF: cerebrospinal fluid; ENA: ; GBS: Guillain-Barré
26 syndrome; HCV: hepatitis C virus; HIV: human immunodeficiency virus; HP: histopathology; HTLV-
27 1: human T-lymphocyte virus type 1 ; MAG: ; MRI: magnetic resonance imaging; NCS: nervous
:F
28 conduction study; RF: rheumatoid factor; SSEP:

29
or
30
31
32 Features of vestibular ataxia are vertigo, nystagmus, impaired balance in stand and gait, oscillopsia
33 (illusion of movement of the visual world due to spontaneousness of the eyes) with or without
Re
34 autonomic manifestations. These symptoms and signs, contrary to sensory ataxia, are equal with
35
36 open or closed eyes (Romberg test). (105) Clinical practice will be a challenge differentiating that to
vie
37 cerebellar ataxia and distinguish peripheral and central etiologies, using HINTS maneuvers: Head
38 Impulse test, Nystagmus, Test of Skew; with or without auditory tests (HINTS plus) or the “Triage-
39
TiTrATE-Test method” (106)
40
w
41
42 ● Triage: Identify obvious dangerous causes by the presence of prominent associated
43 symptoms, abnormal vital signs, altered mental state, or ancillary test results.
On
44 ● Timing: narrow the differential diagnosis by classifying the dizziness attack pattern as
45
46 episodic, acute, or chronic in duration in the history of present illness.
47 ● Triggers: seek an underlying pathophysiologic mechanism by search for obvious triggers or
ly
48 exposures in the review of systems.

49
● Targeted Exam: differentiate benign versus dangerous causes within a timing-trigger
50
51 category using specific bedside findings, emphasizing a targeted eye movement exam.
52 ● Test: choose the best laboratory or imaging test when there is clinically relevant residual
53 uncertainty about a dangerous cause that has not been ruled out.
54
55
56
57
58
59
1
2
3 Myopathic syndrome
4
5 Myopathies are disorders that affect the structure, channels, or metabolism of the skeletal muscle.
6 The clinical presentation of myopathies include negative symptoms such as weakness, fatigue,
7
exercise intolerance and muscle atrophy, as well as positive symptoms as contractures, cramps,
8
9 myalgias, stiffness and myoglobinuria. The classic clinical pattern of myopathy is proximal symmetric
10 weakness. The most frequent symptom in a patient with myopathy is weakness. Pain is not common
11 in most muscle diseases unless it is an inflammatory myopathy or myositis (constant); or in
Co
12 metabolic myopathies (episodic). The most important differential diagnosis are disorders of the
13
14
neuromuscular plaque. (108) Barohn et al described 10 clinical patterns of weakness to approach
nf
15 myopathies (Table 7): (109)
16
17
ide
Weakness
18 Pattern Diagnosis
Trigger
19
Proximal/Distal Symmetry Episodic
20
21
nt
Pattern 1: Limb-Girdle Proximal Symmetric ----- ------ Most myopathies
22 (hereditary and acquired)
23
24
ial
Pattern 2: Distal Distal Symmetric ----- ------ Distal myopathies

25 (overlap with
26 neuropathies)
27
:F
28 Pattern 3: Proximal Proximal arm Facioscapulohumeral ----- ------ Facioscapulohumeral

29 arm/distal leg and distal leg symmetric dystrophy, Emery-
or
30 Dreyfuss, acid maltase.

31
32 Pattern 4: Distal Proximal Asymmetric ----- ------ Inclusion body myositis,
33 arm/proximal leg myotonic dystrophy
Re
34
35 Pattern 5: Proximal Asymmetric ----- ------ Oculopharyngeal
36 Ptosis/ophtalmoplegia (myasthenia) dystrophy, myasthenia
vie
gravis, myotonic
37
dystrophy, mitochondrial
38
39
Pattern 6: Neck extensor Proximal ------- ----- ------ Isolated neck extensor
40
w
myopathy, myasthenia
41 gravis (overlap with ALS)
42
43
On
Pattern 7: Bulbar Proximal ------- ----- ------ Myasthenia gravis,

44 Lambert-Eaton,
45 Oculopharyngeal
46 dystrophy
47
ly
48 Pattern 8: Episodic Proximal ------- Yes Yes McArdle, carnitine

49 weakness/pain/RM + palmitoyl transferase,
50 trigger drugs, toxins.
51
52 Pattern 9: Episodic Proximal ------- Yes May Primary periodic
53 weakness unrelated to paralysis,
exercise channelopathies
54
55
56
57
58
59
1
2
3
4 Pattern 10: ------ -------- Yes May Myotonic dystrophy, stiff
5 Stiffness/inability to person, neuromyotonia
6 relax
7
8 Table 7. Clinical patterns of muscle disorders. RM: rhabdomyolysis, ALS: amyotrophic lateral
9 sclerosis. Modified from Jackson C, et al. RM: rhabdomyolysis, ALS: amyotrophic lateral sclerosis.
10
11
Co
Identifying the pattern of weakness can help to orient further evaluation. The principal etiologies
12
13 are mentioned in the previous table.
14
nf
15
16 Myasthenic syndrome
17
ide
18 Myasthenic syndrome is characterized by weakness due to neuromuscular plaque impairment. The
19
type and location of weakness is variable, but most cases present a feature known as fatigability.
20
21 This means that strength diminishes as the day passes or after physical activity and improves with
nt
22 rest. Strength may also fluctuate during the day. (110)

23
24 The most common initial presentation involves the extraocular muscles but can present with bulbar
ial
25 muscle or generalized weakness. Other less frequent presentations for myasthenic syndrome are
26 proximal muscle weakness and jaw muscle weakness. Ocular weakness causes ptosis and diplopia.
27
:F
As it is a neuromuscular plaque disorder, sensitive examination is normal. Deep tendon reflexes are
28
29 normal, unless there is a chronic severe myopathic process with muscle atrophy, where reflexes
may be diminished or absent. (111)
or
30
31
32 Diseases presenting as myasthenic syndrome are myasthenia gravis (MG) and Lambert-Eaton
33 syndrome (LEMS). (112) Ancillary tests as neuromuscular plaque antibodies, repetitive nerve
Re
34 stimulation and single fiber electromyography are helpful to differentiate MG and LEMS. MG
35 typically presents positive ACh-receptor antibodies (or anti-Musk or LRP-4), and electrodecrement
36
in low frequency repetitive nerve stimulation. LEMS is a disorder characterized by diminished ACh
vie
37
38 release from the presynaptic terminal. It is diagnosed with anti-P/Q-type voltage-gated calcium
39 channel antibodies and high frequency repetitive nerve stimulation with postactivation facilitation.
40 (113)
w
41
42
43
On
44 Neuropathic syndromes
45
46 Neuropathies are a group of diseases that affect the peripheral nervous system (PNS). The PNS
47 includes motor, sensory and autonomic nerves. Neuropathies can localize to the nerve roots (see
ly
48 radiculopathy syndrome), dorsal ganglia (ganglionopathy), peripheral motor nerve body

49 (neuronopathy, see lower motor neuron syndrome) or axon. Neuropathy affecting one nerve is
50
51 known as mononeuropathy, if it affects two or more non-contiguous nerves it is called a
52 mononeuropathy multiplex, and if there several nerves affected it is called polyneuropathy. (114)
53
54 Thus, peripheral neuropathies present with motor symptoms such as weakness (mainly distal) ,
55 atrophy and hypotonia depending on the distribution of the affected nerve; sensory symptoms such
56 as altered vibration sensation, joint position sense and 2 point-discrimination; and autonomic
57
58
59
1
2
3 symptoms as orthostatic hypotension, constipation, neurogenic bladder, erectile disfunction and
4
sweating abnormalities. If the small fibers are injured, patients present with burning and tingling
5
6 sensation, electric shocks, hyperalgesia, or allodynia. (115)
7
Polyneuropathies can be divided in acute, subacute, and chronic according to temporal evolution.
8
9 Acute consists in evolution in less than 4 weeks, where Guillain Barré syndrome is the prototype
10 disease. Subacute polyneuropathies present in 4-8 weeks and chronic polyneuropathies go beyond
11 8 weeks.
Co
12
13 Also, depending on the distribution, neuropathies can be classified into two categories: length
14 dependent and non-length dependent neuropathies. The most common is length dependent, which
nf
15
presents a distal and symmetric distribution with sensory symptoms such as anesthesia or tingling,
16
17 which usually precede motor weakness and often becomes evident when the symptoms progress
ide
18 to the knee. This pattern Is present in metabolic neuropathies, such as diabetic. In non-length
19 dependent neuropathies, the motor involvement is much more evident and involves both proximal
20 and distal limbs. Also, reflexes are globally reduced or absent, as is the case of polyneuropathies.
21
nt
Non-length dependent neuropathies etiologies include sarcoidosis, amyloidosis, neoplastic,
22
23 paraneoplastic, vasculitic, infectious, and inflammatory immune-mediated causes. (116) As in
24 myopathic syndromes, Barohn et al divided neuropathies according to clinical patterns (Table 8).
ial
25 (117)
26
Weakness Sensory Severe UMN Autonomic Diagnosis
27
:F
Proximal Distal Asymmetric Symmetric symptoms proprioceptive signs signs/symptoms

28 loss
29 Pattern 1: + + + + GBS/CIDP
or
Symmetric
30 proximal and
31 distal
32 weakness with
sensory loss
33
Re
Pattern 2: + + + CSPN, metabolic,

34 distal sensory drugs, hereditary
35 loss
with/without
36 weakness
vie
37 Pattern 3: + + + Vasculitis, HNPP,

distal MADSAM,
38 weakness with mononeuropathy,
39 sensory loss radiculopathy
40 Pattern 4: + + + + Polyradiculopathy,
w
asymmetric plexopathy
41 proximal and
42 distal
weakness with
43
On
sensory loss
44 Pattern 5: + + +
45 asymmetric UMN & LMN: ALS
distal
46 weakness
47 without UMN only: PLS
ly
sensory loss LMN only: MMN,

48
PMA, BAD, LAD,
49 MAMA
50 Pattern 6: + + + + + B12 deficiency,
symmetric copper deficiency,
51 sensory loss Friedrich ataxia,
52 and upper adrenomyelo-
53 motor neuron neuropathy
signs
54 Pattern 7: +/- + + SMA and
55 symmetric hereditary motor
weakness neuropathy
56
57
58
59
1
2
3 without
sensory loss
4 Pattern 8: + (neck + + ALS
5 focal midline extensor
6 proximal and
symmetric bulbar)
7 weakness
8 Pattern 9: + + + Ganglionopathy
9 asymmetric
proprioceptive
10 loss without
11
Co
weakness
Pattern 10: + HSAN, diabetes,
12 autonomic GBS, amyloid,
13 disfunction porphyria and
14 Fabry
nf
15 Table 8: Clinical patterns of neuropathic disorders. Obtained from Barohn et al.
16
17 Abbreviations: ALS, amyotrophic lateral sclerosis; BAD, brachial amyotrophic diplegia; CIDP, chronic
ide
18 inflammatory demyelinating polyneuropathy; CSPN, cryptogenic sensory polyneuropathy; GBS,
19 Guillain-Barre´ syndrome; HNPP, hereditary neuropathy with liability to pressure palsy; HSAN,
20 hereditary sensory and autonomic neuropathy; LAD, leg amyotrophic diplegia; MADSAM, multifocal
21
nt
acquired demyelinating sensory and motor; MAMA, multifocal acquired motor axonopathy; MMN,
22
23 multifocal motor neuropathy; PMA, progressive muscular atrophy; SMA, spinal muscular atrophy;
24 UMN, upper motor neuron.
ial
25
26 The most common are patterns 1 and 2. Pattern 1 is the classical GBS and CIDP presentation, while
27 pattern 2 is secondary to metabolic abnormalities and drugs, and usually presents with symmetrical
:F
28 distal sensory loss with or without motor involvement. Etiologies of each pattern are mentioned in
29
the previous table.
or
30
31
32
33 Radicular syndrome
Re
34
35 Radiculopathy is a term used to describe disorders of the nerve roots. The sensory fibers enter to
36 the spinal cord from the periphery as dorsal roots, while the motor fibers exit the ventral horns as
vie
37
ventral roots. Radiculopathies exhibit a segmental distribution of sensory and motor signs and
38
39 symptoms. (118)
40
w
41
Dorsal root lesions result in irritative or negative sensory abnormalities. The principal symptom is
42 radicular pain, which is described as irritative, electric or burning, sharp and well localized to a
43 specific dermatome. Negative sensory abnormalities include hypo or anesthesia. Pain is generally
On
44 the first manifestation of a dorsal root disorder and may be elicited by maneuvers that increase
45 intraspinal pressure or stretch nerve roots, such as coughing, sneezing, Valsalva, or Spurling,
46
47 Lasegue and Bragard signs. (119)
ly
48
On the other hand, ventral root lesions result in negative motor symptoms, such weakness and
49
50 atrophy. Weakness comprehends the myotomal distribution of the affected root. To differentiate
51 from lower motor neuron diseases, ventral root injuries present with less severe atrophy and none
52 or minimal fasciculations.
53
54 Movements to include in the upper extremities should include the following: shoulder abduction
55 (C5, axillary), elbow flexion (C5/C6, musculocutaneous), elbow extension (C6/C7, triceps), wrist
56
57
58
59
1
2
3 extension (C6/C7, radial), finger extension (C7/ C8, radial), wrist flexors and pronators (C6/7,
4
median/ulnar), distal thumb flexors (C8, median), and finger abduction (C8/T1, ulnar). In the lower
5
6 extremities, the following movements should be included: hip flexion (L1/ L2, femoral), hip
7 abduction (L5, superior gluteal), hip adduction (L2/L3/L4, obturator), knee extension (L2/L3/L4,
8 femoral), knee flexion (L5/S1, sciatic), ankle dorsiflexion (L4/L5, deep fibular), ankle inversion (L5,
9
10 tibial), toe extension (L5, deep fibular), and plantarflexion (S1/S2, tibial). (120)
11
Co
12 Also, if the reflex arc is affected by the segmental distribution of dermatomes or myotomes, it may
13 present with segmental hypo or areflexia.
14
nf
15 Radicular syndromes are highly topographic, due to the corresponding root innervation.
16 Electrodiagnostic testing is particularly useful to confirm radicular involvement, especially late
17
ide
responses such as F waves and H reflex. (121)
18
19 Causes of radicular syndromes include: mechanical compression of the nerve roots (degenerative,
20
21 traumatic, congenital), infectious (e.g. herpetic radiculitis), neoplastic, infiltrative, and autoimmune
nt
22 (e.g. Guillain-Barré syndrome). Guillain-Barré usually presents as a polyradiculoneuropathy

23 syndrome, which presents with clinical symptoms and signs of both polyneuropathic and radicular
24
ial
syndromes.
25
26
27
:F
28
29 Spinal cord syndromes
or
30
31 The spinal cord consists of ascending and descending tracts that connect the encephalon with the
32
33 peripheral nervous system. (122) The most representative tracts because of their clinical features
Re
34 are the: corticospinal, spinothalamic, and dorsal column tracts. Corticospinal lesions in the spinal
35 cord present with ipsilateral weakness, spinothalamic lesions cause contralateral pain and
36
temperature sensation loss and dorsal column lesions cause ipsilateral vibration, proprioception and
vie
37
38 two-point discrimination sensation loss. (123) Other tracts are more difficult to assess clinically. The
39 following are the most common recognized spinal cord syndromes:
40
w
41 Complete cord transection syndrome

42
43
On
44 In complete cord transection syndrome, all sensory and motor pathways are disrupted. Patients
45 present with a complete sensory level, one or two segments below the level of the injury. Bilateral
46 upper motor neuron weakness and autonomic dysfunction are also seen. In an acute phase a flaccid
47
ly
paralysis and flaccid autonomic dysfunction may occur. Over time, spasticity and hyperreflexia will
48
49 develop in the level of the injury. Acute spinal cord transection is most caused by trauma; other
50 causes include infarction, demyelinating disease, tumors, infection, hemorrhage, and acute disc
51 herniation. (124)
52
53
54 Brown-Sequard (Hemicord) syndrome
55
56
57
58
59
1
2
3 In an hemicord injury, there is ipsilateral upper motor neuron weakness and vibration and position
4
sensation loss below the level of the injury. Contralaterally, there is pain and temperature sensation
5
6 loss two segments below the level of injury. Some cases may include complete vibration and
7 position sensation impairment or signs that suggest extension to the other half of the spinal cord.
8 The Brown-Sequard plus is an appropriate term for those cases. Causes include penetrating injuries
9
10 or trauma, demyelinating lesions, tumors or infection.
11
Co
12 Central cord syndrome
13
14 Small, central lesions damage the spinothalamic fibers crossing in the anterior commissure causing
nf
15
a suspended sensory loss to pain and temperature often involving the lateral aspect of both limbs.
16
17 In cervical lesions this is called cape distribution. Sacral sparing (at least early) is common due to
ide
18 sacral fibers lateral localization. As the central lesion grows, damaged anterior horn cells produce
19 lower motor neuron deficits with upper motor neuron signs. Central cord syndrome is typically seen
20
21 in syringomyelia and intrinsic spinal cord tumors (i.e. hemangioblastoma, ependymoma).
nt
22
23 Posterior column syndrome
24
ial
25 In isolation, lesion to the posterior column causes impairment of the vibration and proprioception
26
with sensory ataxia. Cervical involvement may also present a Lhermitte sign. Deep tendon reflexes
27
:F
28 may be normal or decreased (if there is nerve root involvement). The classical disease associated
29 with posterior column syndrome is tabes dorsalis due to neurosyphilis.
or
30
31 Posterolateral syndrome
32
33
Re
34 This syndrome involves the posterior columns and the lateral corticospinal tracts. Therefore,
35 patients have vibration and position sensation loss and upper motor neuron weakness. Pain and
36 temperature sensation is spared. This syndrome is typically seen in vitamin B12 deficiency but can
vie
37
also be seen in copper deficiency or metabolic myelopathies.
38
39
40 Anterior horn syndrome
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41
42 Damage to anterior horn cells causes flaccid weakness, atrophy, fasciculations with reduced or
43 absent reflexes and absent sensory impairment. Polio is the classic example of anterior horn
On
44
45 syndrome, but since eradication viruses such as West Nile and Japanese encephalitis virus have been
46 identified as causes. In children, spinal muscular atrophy is the most important cause of anterior
47 horn syndrome.
ly
48
49
Combined anterior horn and corticospinal tract disease
50
51
52 It features a combination of upper motor neuron and lower motor neuron signs with sparing of the
53 sensory function. This distinctive pattern without sensory impairment is highly suggestive of motor
54 neuron disease. Other causes include cervical myelopathy.
55
56
57
58
59
1
2
3 Anterior cord syndrome
4
5
Most seen with anterior spinal artery injury. Due to the irrigation of this artery, the anterior two-
6
7 thirds of the spinal cord are affected. Patients will have bilateral upper motor neuron weakness
8 because of anterior corticospinal tract and anterior gray matter involvement, and loss of pain and
9 temperature below the level of the lesion because of affection to the anterolateral system. Some
10
11 patients can have trouble with movement coordination by partial involvement of the
Co
12 spinocerebellar tract.
13
14 Because dorsal columns are not affected, patients will preserve proprioception and vibration
nf
15
functions.
16
17
ide
18 Cauda equina and conus medullaris syndromes
19
20 Cauda equina syndrome results from the dysfunction of multiple sacral and lumbar nerve roots in
21 the lumbar vertebral canal. Conus medullaris syndrome results when there is compressive damage
nt
22
23 to the spinal cord from T12-L2. It presents with early flaccid bladder dysfunction and bilateral
24 “saddle” sensory loss. Cauda equina syndrome presents with radicular pain, with late bladder,
ial
25 bowel or sexual dysfunction and perianal or “saddle” numbness. Timing of pain and bladder
26
dysfunction are helpful to differentiate conus medullaris and cauda equina syndromes, although in
27
:F
28 most cases can be virtually impossible to differentiate clinically. (125)

29
or
30
31
32 Upper motor neuron syndrome (pyramidal or corticospinal syndrome)
33
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34 The term upper motor neuron was introduced by Sir William Gowers in his manual of neurology in
35
1886. (126) The upper motor neuron includes crossed and uncrossed corticospinal tracts,
36
vie
37 corticobulbar, tectospinal, rubrospinal, vestibulospinal and reticulospinal tracts, as well as various

38 short internuncial and cerebellar connections that play a role in motor (voluntary motor control,
39 control of posture and gait) and non-motor control (modulation of sensory input and motor output
40
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41 of the spinal cord). (127, 128)

42
43 Lesions in components of the upper motor neuron pathway from the cortex (principally in the
On
44 frontal lobe, but can be presented in lesions of the parietal, temporal and occipital lobe), corona
45
46
radiata, internal capsule, brainstem, and white matter of the spinal cord produce an upper motor
47 neuron syndrome. (129) Upper motor weakness manifests initially as a flaccid paresis, but
ly
48 eventually becomes spastic and is accompanied by hypertonia and hyperreflexia. The upper motor
49 neuron syndrome is associated with the presence of pathologic reflexes and signs, especially an
50
51 extensor plantar reflex or Babinski’s sign.
52
53 To be more specific in the upper motor neuron syndrome localization, we use the following clinical
54 terms in clinical practice:
55
56
57
58
59
1
2
3 ● Dense: Medical Research Council (MRC) strength ≤3 in the most affected limb. If strength is
4
4 or 5, the upper motor neuron syndrome is non-dense.
5
6 ● Proportionate: strength has a ≤2 points difference in the MRC score between the upper and
7 lower ipsilateral limbs. If there is a difference of 3 or more points, the upper motor neuron
8 syndrome is disproportionate.
9
10 ● Complete: the patient presents an extensor plantar response. It is called incomplete if the
11 plantar response demonstrates flexion.
Co
12
13 These terms help to determine a more precise localization. For cortical lesions, patients usually have
14
non-dense, disproportionate upper motor weakness. If the arm is more affected than the leg, lesions
nf
15
16 are often laterally placed on the contralateral cortico-subcortical hemisphere. If the leg is more
17 affected than the arm, then the lesion is most likely in the contralateral paracentral region.
ide
18
19 In internal capsule lesions, lesions are dense and proportionate, and mostly cause a pure motor
20
21 hemiplegia. In some cases, depending on the extension of the lesion, it can be accompanied by signs
nt
22 from involvement of neighboring structures such as sensory loss (thalamogeniculate segment) or

23 hemianopia (optic tract). Brainstem lesions typically cause “crossed” syndromes involving ipsilateral
24
ial
cranial nerve affection and upper motor weakness contralateral to the lesion. Thus, a dense
25
26 presentation of an upper motor neuron suggests a lesion involving the internal capsule, brainstem,
27 or spinal cord. (130)
:F
28
29
or
30 Lower motor neuron syndrome

31
32 Lower motor neuron syndrome is often misdiagnosed as neuropathy. Although both present similar
33 clinical characteristics, the lower motor neuron syndrome implies neuron body injury, or
Re
34
35
neuronopathy, while neuropathy to peripheral nerve axons. This is an important concept, as lower
36 motor neuron disease approach is different than a neuropathic approach. Lower motor neuron
vie
37 syndrome presents with flaccid weakness, muscle atrophy, fasciculations and hyporeflexia. There
38 should be no sensitive involvement in lower motor neuron syndrome. The presence of early
39 fasciculations should raise suspicion for neuron body involvement, rather than the axon. (131) Table
40
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41
9 enlists the differences between upper and lower motor neuron syndromes.
42
43 Clinical evaluation should consider temporal characteristics as onset and progression, pattern of
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44 weakness (symmetric/asymmetric, proximal/distal, upper/lower limb involvement and

45 presence/absence of bulbar involvement), the presence/absence of sensory and/or autonomic
46
47 abnormalities, a family history of a similar disorder and toxic exposition history. (132) Nerve
ly
48 conduction studies and electromyography show characteristically a neurogenic pattern. Some other
49 clues as the presence of fasciculations should orient our topographic diagnosis to the neuron body.
50
Moreover, in nerve conduction studies, there is sensitive-nerve sparing.
51
52
53 LMN syndromes can be divided in sporadic or genetic. Sporadic presentation should orient the
54 clinician to diseases as amyotrophic lateral sclerosis (ALS), progressive muscular atrophy, multifocal
55
56
57
58
59
1
2
3 motor neuropathy, Hirayama disease and polio. Genetic causes include Kennedy disease, distal
4
hereditary motor neuropathy and spinal muscular atrophy. (133, 134)
5
6 Feature UMN LMN
7 Muscle tone Spasticity Flaccid
8 Atrophy No atrophy (disuse) Atrophy
9 Deep tendon reflexes Hyperreflexia Hyporeflexia or areflexia
10 Plantar response Extensor Flexor
11 Superficial reflex Absent Present
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12 Fasciculations Absent Present
13 Table 9. Differences between upper motor neuron (UMN) and lower motor neuron (LMN)
14
syndromes.
nf
15
16
17
ide
18 Dysautonomic syndromes
19
20 The autonomic nervous system is part of the efferent division of the peripheral nervous system. It
21 adapts the organism to internal and external changes, maintaining body homeostasis and
nt
22 coordinating responses. (135) Clinical approach may be divided depending on the part of the
23
nervous system involved. The sympathetic nervous system comprises noradrenergic, adrenergic,
24
ial
25
and cholinergic systems. On the other hand, the parasympathetic nervous system involves the
26 brainstem and sacral spinal cord. Considering these, there are specific clinical syndromes that can
27 be recognized (Table 10): (136)
:F
28
Sympathetic Parasympathetic
29
Function Noradrenergic Adrenergic Cholinergic Cranial Sacral
or
30
31 Decreased -Orthostatic -Fatigue Decreased -Dry mouth -Urinary retention
32 hypotension -Hypoglycemia sweating -Mydriasis -Male erectile
33 -Lack of -Constipation failure
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34 tachycardia
35 -Horner
36 syndrome
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37 Increased -Palpitations -Palpitations Increased -Salivation -Nausea

38 -Increased -Increased systolic sweating -Bradycardia -Urinary
39 systolic blood blood pressure -Bronchial frequency
40 pressure -Tachycardia constriction -Increased
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41 -Tachycardia -Mydriasis -Miosis gastrointestinal

42 -Mydriasis -Sweating -Lacrimation transit
43 -Sweating -Cold hands
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44 -Cold hands -Slowed

45 -Salivation gastrointestinal
46 -Piloerection transit
47 -Anxiety
ly
48 -Tachypnea
49 -Bronchial dilation
50 -Hyperglycemia
51 Table 10. Characteristics of Dysautonomic syndromes.
52
53 It is difficult to precise a topographic diagnosis with a pure autonomic syndrome. Defining
54 autonomic syndromes is useful to approach diseases that have multiple syndromes in which the
55
autonomic system is affected such as hypothalamic tumors, brainstem, or spinal cord syndromes.
56
57
58
59
1
2
3
4
5 Cerebellar syndromes
6
7 The cerebellum is a complex part of the brain that functions as a co-processor of movement, working
8 in concert with the cerebral cortex and basal ganglia. (137) It is also involved in sensorimotor
9 operations, cognitive tasks, and affective processes. Anatomically, the cerebellum is composed of
10
11 two hemispheres (left and right) divided by a midline structure called vermis. It is also divided into
Co
12 three lobes: anterior, posterior and flocculonodular lobes. The primary fissure separates the
13 cerebellum into an anterior lobe and a posterior lobe, while the posterolateral fissure separates the
14 posterior lobe and the flocculonodular lobe. The lateral hemispheres are involved in motor planning
nf
15
for extremities and distal limb coordination. The vermis is involved in axial coordination and balance,
16
17 while the flocculonodular lobe oversees vestibulo-ocular reflexes. (138) Cerebellar syndromes are
ide
18 highly localizable. Based on the anatomical divisions, the cerebellar syndromes are grouped in four
19 (Table 11): (139)
20
21 ● Rostral vermis syndrome (anterior lobe)
nt
22 ● Caudal vermis syndrome (flocculonodular and posterior lobe)

23 ● Hemispheric syndrome (anterior and posterior lobes)
24
ial
● Pancerebellar syndrome (all lobes)

25
26 The rostral vermis syndrome includes a wide-based stance and titubating gait, ataxia of gait, normal
27
:F
28 or slightly impaired limb coordination and minimal hypotonia, nistagmus or dysarthria. The most
29 common cause is alcoholic degeneration. (140)
or
30
31 The caudal vermis syndrome includes axial disequilibrium, staggering gait with little or no limb
32 ataxia. It may produce spontaneous nystagmus associated with damage to the flocculonodular lobe.
33 The most common causes are tumors (e.g. medulloblastoma in children) or metastasis. (141)
Re
34
35 The hemispheric syndrome presents with appendicular ataxia. It affects fine motor coordination,
36 typically presenting altered finger-to-nose testing, heel-to-shin testing, and other traditional
vie
37 cerebellar maneuvers. Typically, clinical manifestations are ipsilateral to the affected cerebellar
38
39 hemisphere. The most common causes are infarction, abscesses, tumors (primary and metastasis)
40 and demyelinating diseases.
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41
42 The pancerebellar syndrome is a combination of the previous three syndromes. Patients present
43 axial and appendicular ataxia, nistagmus, dysarthria and altered balance. The most common
On
44 etiologies are toxic-metabolic disturbances, such as hypoglycemia, hyperammonemia and

45 hyponatremia. Phenytoin, carbamazepine, and valproic acid are drugs associated with
46
Pancerebellar disturbances. (142, 143) Other causes include infections, as in cerebellitis, and
47
ly
48 paraneoplastic degeneration. (144)

49
Syndrome Symptoms Etiologies
50
51 Rostral vermis +Wide-based stance and titubating Alcoholic degeneration
52 syndrome gait
53 +Ataxia of gait
54 +Normal or mildly affected limb
55 coordination
56
57
58
59
1
2
3 +Infrequent hypotonia, nystagmus
4 and dysarthria
5 Caudal vermis +Axial disequilibrium and Primary tumors (e.g. medulloblastoma),
6 syndrome staggering gait metastasis.
7 +Little or no limb ataxia
8 +Spontaneous nystagmus and
9 ocular dysmetria
10 Hemispheric +Incoordination of ipsilateral limb Infarcts, Neoplasms, abscess, demyelinating
11
Co
syndrome movements (altered finger-nose, diseases.
12 heel-to-shin and altered agonist-
13
antagonist coordination)
14
Pancerebellar +Axial and appendicular ataxia Infections, metabolic alterations (e.g.
nf
15
syndrome +Spontaneous nystagmus and hypoglycemia, hyponatremia), paraneoplastic
16
ocular dysmetria cerebellar degeneration, hereditary ataxias (e.g.
17
ide
+Dysarthria SCA) and toxic disorders (e.g. phenytoin,
18
+Altered balance hyperammonemia)
19
20 Table 11. Cerebellar syndromes.
21
nt
22
23
Meningeal syndrome
24
ial
25 The meninges are thin layers that surround the encephalon. They are divided in three: dura mater,
26
arachnoid and pia mater. They act as a barrier for protection, and also work as facilitators for the
27
:F
28 movement of fluid, solutes and cells at the surface of the CNS and in the parenchyma. (146)
29 Inflammation or damage produces pain, thickening and hardening of the affected meningeal
or
30 membranes. This translates into specific signs and symptoms.

31
32 Thus, a meningeal syndrome, also known as meningismus, consists of presence of nuchal rigidity
33 and other clinical signs of meningeal inflammation, usually associated with headache. It is important
Re
34
to differentiate meningeal syndrome from the classical meningitis triad: fever, nuchal rigidity and
35
36 altered mental status. (147) This triad was described in patients with acute bacterial meningitis and
vie
37 considers altered mental status as part of it. As we discussed previously, altered mental status is
38 considered as a part of encephalopathy. Thus, syndromically, this triad comprehends a combination
39 of syndromes: a meningoencephalopathy or a meningoencephalitic syndrome.
40
w
41 There are several signs that were described in meningeal inflammation. Nuchal rigidity is the most
42 widely recognized and frequently encountered sign of meningeal irritation. It is characterized by
43
On
44
stiffness and spasm of the neck muscles, mainly extensors. This causes pain on attempted voluntary
45 movements of the neck as well as resistance to passive movement. As extensors are the primary
46 muscles affected, the initial finding is resistance to passive neck flexion.(148) Other classic clinical
47 signs described in meningeal irritation are Kernig’s and Brudzinski’s, both have good specificity (90-
ly
48 96%) but with low sensitivity (50-57%). The classic Kernig sign described an involuntary flexion of
49
50 the knee when the hip is flexed with the knee extended. The Brudzinski sign consists of flexion of
51 the knees when the examiner flexes the neck while holding down the patient’s chest with one hand.
52 The most sensible sign is jolt accentuation, which consists in exacerbation of headache when the
53 head is rotated with a frequency of 2-3 times per second in the horizontal axis. The reported
54
sensibility for jolt accentuation is 97-100%, with a 54-60% specificity. (149,150) Many other
55
56
57
58
59
1
2
3 meningeal signs have been described, nonetheless, they have not shown better diagnostic accuracy
4
than the signs described earlier.
5
6 Precise topographic meningeal syndrome diagnosis is difficult. Etiologies related with meningeal
7
syndrome include: infectious meningitis (bacterial, viral, fungal and parasitic), neoplastic meningitis,
8
9 autoimmune meningitis (Systemic lupus erythematosus, Rheumatoid meningitis, Behcet, IgG4,
10 histiocytosis and Neurosarcoidosis) and the presence of blood in subarachnoid space (e.g.
11 subarachnoid hemorrhage). (151)
Co
12
13
14
nf
15 Conclusion
16
17 The syndromic approach in patients with a neurological disease is a powerful tool that can help the
ide
18 clinician obtain a correct and timely diagnosis. To apply this approach, the clinician must be familiar
19 with the main neurological syndromes. Even though most of them were described centuries ago,
20 their usefulness has not diminished.
21
nt
22 When coupled with the disease progression and the basic past medical history, the main
23
neurological syndromes can help establish a diagnostic pathway in most of the patients. This can
24
ial
25 help the clinician avoid uncertainty when approaching to a patient with a neurological complain.
26
27
:F
28 References
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Complete List of Authors: Galnares-Olalde, Javier; Instituto Nacional de Neurologia y Neurocirugia

Medina-Rioja, Raul; Instituto Nacional de Neurologia y Neurocirugia

Saldívar-Dávila, Sergio; Instituto Nacional de Neurologia y Neurocirugia

Neurocirugia Manuel Velasco Suarez, Neurology

Manuel Velasco Suarez, Neurology

Keywords: CLINICAL NEUROLOGY

22 Alvarado-Bolaños Alonso Alejandro

25 confused with delirium. Encephalopathy is mostly used by neurologists or internal medicine

48 Hyperacute Acute Subacute Chronic

22 defined by clinical, imaging, and electroencephalographic criterion. (7) Venkatesan et al proposed a

the following: (8)

30 ≥24 h with no alternative cause identified.

34 o Documented fever ≥38° C (100.4°F) within the 72 h before or after presentation

37 o CSF pleocytosis (WBC count ≥5/cubic mm)

41 o Abnormality on electroencephalography that is consistent with encephalitis and not

44 As in the case of encephalopathy, localization is nonspecific in encephalitis, as it represents a diffuse

22 consciousness as part of encephalopathy or seizure, there is no specific localization. If part of

28 these are hemorrhage, infarction, trauma, or infection. (12)

communication (reading and writing). Non-linguistic components of language as emotion,

Global - - - - - - Right faciobrachial Perisylvian cortical

48 /+ (mild) (mild) fluctuation, right putamen,

34 call it “pseudosociopathy” or “acquired sociopathy”, because patients present with impulsivity,

41 Medial prefrontal syndrome

25 language, perceptual–motor, or social cognition) based on:

28 has been a significant decline in cognitive function; and

30 standardized neuropsychological testing or, in its absence, another quantified

41 interhemispheric fibers and the sympathetic apraxia by disruption in the interhemispheric

22 Pregnancy or puerperium Headaches attributed to cranial or cervical vascular disorders; postdural

cerebral sinus thrombosis; hypothyroidism; anemia; diabetes denial or

28 features Hunt syndrome; ophthalmic causes

34 Painkiller overuse or new Medication overuse headache; drug incompatibility

41 Seizure (Convulsive) syndrome and epilepsy

22 Focal to bilateral tonic-clonic Unclassified

34 neurobiological, cognitive, psychological, and social consequences of this condition.

by demyelinating disorders, infarction, trauma, hemorrhage, or infections.

● Combined abducens nucleus, medial longitudinal fasciculus and paramedian pontine

37 infarction, tumor, hemorrhage, or trauma. (52)

Medial superior pontine

22 Cavernous sinus syndrome

22 cause are mastoid infections, followed by petrous apex tumors. (77)

34 Jugular foramen syndromes and lower cranial nerves syndromes

surgery and fractures of the skull base (Table 5). (80-81)

22 trapezius and and sympathetic

28 parkinsonism-ALS and parkinsonism-FTD. (92)

37 vestibular. Cerebellar ataxia is the most common. (96)

41 hereditary ataxias, and non-hereditary degenerative ataxias. Classic clinical manifestations

25 Peripheral Acute -Miller Fisher syndrome -Anti-GQ1b antibodies, CSF, NCS

34 -Celiac disease -Anti-tTG antibodies

37 Dorsal root Acute/Subacute -HIV, HTLV-1, HCV -Serology

41 -Chemotherapeutic -History of exposure

-Chronic active hepatitis -RF, ANA, ASMA, hepatitis serology

22 ACE: angiotensin-converting enzyme; ANA: antinuclear antibodies; ASMA: anti-smooth muscle

28 conduction study; RF: rheumatoid factor; SSEP:

48 exposures in the review of systems.

Pattern 2: Distal Distal Symmetric ----- ------ Distal myopathies

28 Pattern 3: Proximal Proximal arm Facioscapulohumeral ----- ------ Facioscapulohumeral

30 Dreyfuss, acid maltase.

Pattern 7: Bulbar Proximal ------- ----- ------ Myasthenia gravis,

48 Pattern 8: Episodic Proximal ------- Yes Yes McArdle, carnitine

22 rest. Strength may also fluctuate during the day. (110)