MOTOR NEURON DISEASES

Anatomy
Route: axons of MN begin in primary motor area internal capsule UMN pons medulla left lateral corticospinal tract or right anterior corticospinal tract LMN (brain stem or in anterior grey horn of spinal cord) SC muscle

WHAT IS AN MND?
diseases that produce dysfunction of the motor neurons, resulting in weakness and muscle wasting etiology = unknown includes conditions that affect the upper (corticobulbar and corticospinal) motor neurons, the bulbar and spinal lower motor neurons or both deadly disease with sporadic cause

 a progressive disorder characterized by:

muscular wasting weakness fasciculation spasticity hyperreflexia extensor plantar responses

no objective sensory signs but may have sensory symptoms

THREE FORMS:
Progressive Muscular Atrophy Progressive Bulbar Palsy Amyotrophic Lateral Sclerosis
(MOST COMMON)

 Disease of the middle life and progress to death in a matter of 2-5 years or longer in exceptional cases

Average age of onset 58 years Uncommon before 40 and after 70

M:Fratio = 1.5:1 (+) family history in 5-10% cases

 Prognosis depends on bulbar involvement: If predominantly bulbar 2.2 years If predominantly spinal 3.3 years Death due to respiratory failure

STRUCTURES PATHOLOGICALLY INVOLVED: motor cortex posterior limb of the internal capsule brainstem and SC corticospinal pathway motor neurons of bulbar nuclei (excluding 3rd, 4th, and 6th nerve nuclei) anterior horns of SC

COMPARISON BETWEEN THE PHYSICAL SIGNS OF MOTOR NEURON DISEASES

EFFECTS Muscle Tone Paralysis Muscle Wastage Superficial Reflex Plantar Reflex Deep Reflex Clonus UMN Hypertonia Spastic type Absent Lost Abnormal (Babinskis sign) Exaggerated Present LMN Hypotonia Flaccid type Occurs Lost Absent Lost Lost

UPPER MOTOR NEURON DISORDERS

Primary Lateral Sclerosis Hereditary Spastic Paraplegia

Primary Lateral Sclerosis

Definition: A rare sporadic disorder of progressive spasticity with mostly spinal and occasionally bulbar region onset sparing the LMN. Epidemiology: Onset of symptoms begins in the 5th decade.

 Etiology: Unknown

Pathophysiology: Betz cells in the primary motor cortex or precentral gyri accompanied by degeneration of the corticospinal pathways

Clinical Manifestations:
Spasticity the most common presenting symptom

Slowly progressive, often symmetric, spastic paraparesis in the legs vs. arms, may progress to involve UE and cranial nerves
Asymmetric limb onset & spasticity involving the UE or bulbar regions are more common manifestations

Decrease sense of balance Clumsy hands Slurred speech Emotional lability Speech and swallowing difficulties Bladder urgenc

Important features: spasticity, hyperreflexia, extensor plantar responses, UMN pattern of weakness
No sensory loss

Prognosis:
the signs of corticospinal tract degeneration betray the presence of ALS will develop indications of LMN disease within 1 year, usually earlier ~ 20% of these patients, however, have a slowly progressive corticospinal tract disorder that begins with a pure spastic paraparesis; later, and to a lesser degree, the arms and oropharyngeal muscles become involved.

Differential Diagnosis:
Multiple sclerosis (for some px who have only restricted bilateral signs of UMN disease) Meningioma Adrenoleukodystrophy Tropical spastic paraplegia HIV myelopathy Strumpell-Lorrain disease

Hereditary Spastic Paraplegia

Definition: UMN disorder; presents most commonly with progressive spasticity, weakness of lower limbs, hypertonic urinary bladder and impaired vibration sense.

A genetically heterogenous group of neurodegenative disorders in which the most severely affected neurons are those of the spinal cord.
AKA Familial Spastic Paraparesis/Strumpell-Lorrain Syndrome

 Epidemiology: Population studies done in Ireland showed a prevalence of 1.27/100,000.

Onset occurs at any age from early childhood to adulthood and progresses slowly over many years without exacerbations, remissions or periods of abrupt worsening.
Most symptoms are experience between the 2nd and 4th decades of life.

Etiology:
Inheritance pattern: autosomal dominant, recessive, and X-linked. 32 HSP loci and 11 HSP-related genes have been identified: classified as spastic gait locus 1 through SPG3

Pathophysiology:
degeneration of the corticospinal tracts throughout the SC, + thinning of the columns of Goll, mainly in the lumbosacral regions, & of the spinocerebellar tracts, even when no sensory abnormalities had been detected during life. Betz and anterior horn cells has also been reported.

Clinical Manifestations:
Pure (classic): slowly progressive spastic paraparesis spasticity most common feature, more disabling than weakness, most predominant in legs increased difficulty in walking sensory and other nervous functions are entirely intact urinary disturbance vibration sense impairment

 In childhood: foot arches become exaggerated, the feet are shortened, & (+) tightening (pseudocontracture) of calf muscles, forcing the child or adolescent to toe-walk In children: the legs appear to be underdeveloped children and adults: quite thin, sometimes the knees are slightly flexed; at other times the legs are fully extended or hyperextended (genu recurvatum) and adducted weakness is variable and difficult to estimate

 Complex:
pure HSP manifestations plus concomitant neurologic disorders: seizures impaired cognition dementia, extrapyramidal disturbance peripheral neuropathy deficits in the absence of other coexisting disorders such as diabetes mellitus

Prognosis:
causes degeneration of the ends of the corticospinal tracts in the SC with progression of the disease caudal to rostral degeneration of the costicospinal tract and mild involvement of the dorsal column occurs.

Differential Diagnosis:
indolent SC or foramen magnum tumor cervical spondylosis (a spinal from of multiple sclerosis) Chiari malformation, compression of the cord by a variety of congenital bony malformations at the craniocervical junction, and a number of chronic myelitides among them are:

lupus erythematosus Sarcoidosis AIDS adrenomyeloneuropathy primary lateral sclerosis tropical spastic paraparesis (caused by HTLV-1)