Gait Problems in Parkinsonism and Frontal Lobe Gait Disorders

Gait Problems in Parkinsonism and Frontal Lobe Gait Disorders
Simon JG Lewis, MD
Brain and Mind Centre, University of Sydney
The assessment of gait is of critical importance for every neurologist and is of particular
relevance in the evaluation of patients in the Movement Disorders setting. Important clues
and diagnostic insights are offered to the keen-eyed observer from the instant that the patient
is collected from the waiting room and relate to far more than just an appreciation of the gait
itself. This overview will offer insights into the critical neuroanatomy underpinning
locomotion, the key changes that can be observed in gait parameters across a range of
parkinsonian and related disorders, as well as highlighting some of the important associated
clinical features that can help to refine diagnostic accuracy and direct therapeutic
management.
The neuroanatomy of locomotion

It is obvious that the neuroanatomical underpinnings of successful locomotion are widespread
and highly integrated across multiple levels of the nervous system including the peripheral
nerves, sensory end organs (e.g. vestibular), muscles/tendons (stretch receptors), spinal cord,
brainstem, cerebellum, basal ganglia, thalamus and cerebral cortex1. Over evolutionary time,
these systems have been combined with other key processes such as the control of posture
and balance, and perhaps more importantly in the context of parkinsonian and frontal lobe
gait disorders, there has been a hierarchical expansion to integrate with higher order centres.
These connections allow for behavioural influences over the more automatic functions that
can occur ‘subconsciously’ within the lower order systems2. This relationship between gait
and higher cognitive functions has been recognised for many years with original work in
Alzheimer’s Disease (AD) describing these patients as having significantly shorter step
length, lower gait speed, lower stepping frequency, greater step-to-step variability, greater
double support ratio and greater sway path than age matched controls3. Thus, it should be
anticipated that the pathological changes occurring in parkinsonian conditions and diseases
affecting the frontal lobe and/or the fronto-parieto-temporo-striatal projections are likely to
manifest with specific gait disturbances especially when additional cognitive processing is
required, such as during dual tasking or when changing a navigational plan (e.g. turning or
negotiating more complex environments).
Whilst the exact details of the neural processes underlying these connections are not fully
understood, it is thought that there are a number of ‘top-down’ influences that can impact
upon the relatively automatic neural reflexes of the spinal cord known as the Central Pattern
Generators. In addition, much interest has concentrated in the medulla and pons of the
brainstem where potential movement patterns may be more easily manipulated in response to
behavioural contingencies. For example, the mesencephalic locomotor region (MLR) of the
brainstem is thought to be mainly involved in the production of movement, whereas the
dorsal pedunculopontine nucleus (PPNd) is associated with the abrupt cessation of
movement. The basal ganglia nuclei are ideally placed to influence these regions by offering
flexibility in response to changing environmental contingencies. At rest, the main output
structures (the globus pallidus internus (GPi) and the substantia nigra pars reticularis (SNr))
provide tonic GABAergic inhibitory tone over the brainstem structures that control gait (such
as the MLR and PPNd) as well as the motor thalamus, effectively constraining information
flow in the spinal cord and cortex, respectively. During activity, cortical input to the basal
ganglia can either relieve (via the striatum) or facilitate (via the subthalamic nucleus; STN)
this inhibitory output. Whilst this allows flexible and volitional control over motor outputs it
Teaching Course 2309 1

obviously represents a critical ‘breakpoint’ where the disseminated pathologies observed
across parkinsonian and frontal lobe disorders can impact upon normal gait.
The spectrum of gait disorder in Parkinson’s Disease

Cleary, Parkinson’s Disease (PD) represents the archetypal Movement Disorder and in turn
forms the basis for our appreciation of the parkinsonian gait. This is of course typified as
being slower with a narrow base, characterised by shorter steps and shuffling. However, the
parkinsonian gait helps to exemplify the breadth of components that should be included in the
fuller assessment of gait disorders. For example, there is an emphasis on whether the posture
is stooped, if arm swing is asymmetric and whether there is en bloc turning where the normal
segmental rotation from head to hips is lost. Furthermore, the ‘parkinsonian’ gait of PD is
often associated with the recognition of other key features such as breakthrough tremor,
festination with ever quickening but shortening steps and of course, Freezing of Gait, which
is most frequently triggered by those additional processing demands alluded to above (e.g.
dual tasking, turning and navigating doorways).
Interestingly, recent work objectively comparing the long established clinical PD phenotypes
of tremor dominant versus postural instability with gait disturbance has demonstrated that
significant overlap exists between many parameters of gait and balance, casting serious doubt
on the clinical utility of this simplistic classification scheme4. Furthermore, there is a growing
appreciation that gait disturbances might represent a subtle ‘pre-clinical’ feature that could
assist in the prediction of those patients with idiopathic Rapid Eye Movement Sleep Behavior
Disorder (iRBD) who are most likely to transition to a neurodegenerative synucleinopathy.
Recent work evaluating gait parameters in iRBD has identified decreased velocity and
cadence, as well as significantly increased double limb support variability and greater
stride/swing time variability compared to age matched controls5. As yet, prospective follow
up data is not available to determine the clinical utility of these observations but home
activity monitoring devices have revealed that incident PD patients are significantly less
active than controls6, highlighting the importance that even subtle gait disturbances should be
targeted early by rehabilitation strategies.
Parkinsonian and Frontal Lobe Gait Disorders

The pathophysiology underpinning parkinsonian and frontal lobe gait disorders is not well
understood and can arise from a range of neurological insults including neurodegenerative
(e.g. Lewy Body Dementia – LBD, Multiple System Atrophy – MSA, Progressive
Supranuclear Palsy – PSP, Corticobasal Syndrome - CBS), cerebrovascular (e.g. Vascular
Parkinsonism, Vascular Dementia - VD) and ‘structural’ (e.g. Normal Pressure
Hydrocephalus - NPH). Perhaps not surprisingly given their more disseminated
neuropathological insults, both LBD and VD have higher rates of gait disorder than
Alzheimer’s with a greater emphasis on balance disturbance7.
The diagnosis of parkinsonian mimics like MSA, PSP and CBS from PD can be clearly very
challenging, especially at the time of the initial presentation. It is well known that many of
the ‘defining’ clinical features of these conditions emerge later in the disease course and
sometimes remain absent. Whilst specific diagnoses may be clinically defined, there is
significant heterogeneity even within recognised disease entities such as the Parkinsonian
(MSA-P), Cerebellar (MSA-C) and Autonomic (MSA-A) variants of MSA or the Pure
Akinesia and Gait Freezing (PAGF) variant of PSP. Attempts to use kinematic gait studies to
distinguish between these parkinsonian conditions have been hampered by the lack of direct
group comparisons and clinicopathological confirmation8. Indeed, recent work has shown

that the final antemortem diagnosis appears incorrect in over a quarter of both PSP and MSA
patients9. The same study revealed that rates of ataxia were similar between PSP (50%) and
MSA (60%) cases, although of course universal in MSA-C. Similarly, falls in the first year
following diagnosis and the occurrence of Freezing of Gait throughout the disease course
were not helpful in distinguishing PSP from MSA. However, non-gait features such as
impairments in saccadic eye movements and apraxia did seem to offer more diagnostic
specificity in favour of PSP. However, it should be appreciated that in the PAGF variant of
PSP, whilst freezing and gait initiation failure are clearly a prominent features there is little in
the way of bradykinesia or rigidity, and the typical eye signs may not be seen or might only
emerge at a late stage10. Atypical features such as apraxia and dystonia may also be seen in
patients with CBS and there is a growing appreciation that such presentations, whilst
clinically similar, may arise from a number of differing neuropathologies including PSP,
MSA, LBD, AD and Frontotemporal Dementia rather than simply all representing tau based
Corticobasal Degeneration11. These more extensive neurodegenerative pathologies along
with other conditions that can impact on more widespread (presumably cortical) networks
such as NPH and small vessel ischaemic lesions, can also manifest with more ‘mutilated’
Frontal Lobe or Higher Level Gait Disorders.
Higher level gait disorders (HLGD) are characterized by various combinations of

disequilibrium and impaired locomotion that are not explained by deficits in strength, tone,
sensation, or coordination12. Their precise neural pathways have not been established but are
likely to include frontal projections to the descending pathways from the brainstem (e.g.
pyramidal, vestibulospinal and tectospinal tracts), along with parietal and temporal regions.
Traditionally, the clinical deficits observed in HLGD have been described as an apraxia of
gait, where these is often an inability to trigger or coordinate normal locomotion. However,
such patients can also struggle to stand from sitting and may be unable to draw out numbers
on the floor using their feet. Given that gait essentially represents a repetitive, stepping
action it has recently been proposed that HLGDs are actually associated with an apraxia of
postural transitions rather than having an apraxia of gait13.
Conclusion
An appreciation of the clinical features associated with parkinsonian and HLGD in relation to
their underlying neuroanatomy can help the clinician with diagnosis, prognosis and
management of these challenging cases.

References
1. Takakusaki K, Tomita N, Yano M. Substrates for normal gait and pathophysiology of

gait disturbances with respect to the basal ganglia dysfunction. J Neurol. 2008;
255:19-29. [PubMed: 18821082]
2. Lewis SJG. Neurological update: emerging issues in gait disorders. J Neurol. 2015;
262:1590-1595. [PubMed: 25736555]
3. Visser H. Gait and balance in senile dementia of Alzheimer's type. Age Ageing. 1983;
12:296-301. [PubMed: 6660138]
4. Herman T, Weiss A, Brozgol M, Giladi N, Hausdorff JM. Gait and balance in
Parkinson's disease subtypes: objective measures and classification considerations. J
Neurol. 2014; 261:2401-2410. [PubMed: 25249296]
5. McDade EM, Boot BP, Christianson TJ, et al. Subtle gait changes in patients with
REM sleep behavior disorder. Mov Disord. 2013; 28:1847-1853. [PubMed:
24130124]
6. Lord S, Godfrey A, Galna B, Mhiripiri D, Burn D, Rochester L. Ambulatory activity
in incident Parkinson's: more than meets the eye? J Neurol. 2013; 260:2964-2972.
[PubMed: 23900754]
7. Allan LM, Ballard CG, Burn DJ, Kenny RA. J Am Geriatr Soc. 2005; 53:1681-1687.
[PubMed: 16181166]
8. Amano S, Skinner JW, Lee HK, et al. Discriminating features of gait performance in
progressive supranuclear palsy. Parkinsonism Relat Disord. 2015; 21:888-893.
[PubMed: 26032992]
9. Xie T, Kang UJ, Kuo SH, Poulopoulos M, Greene P, Fahn S. Comparison of clinical
features in pathologically confirmed PSP and MSA patients followed at a tertiary
center. NPJ Parkinsons Dis. 2015; 1:15007. [PubMed: 28725681]
10. Owens E, Josephs KA, Savica R, et al. The clinical spectrum and natural history of
pure akinesia with gait freezing. J Neurol. 2016; 263:2419-2423. [PubMed:
27624121]
11. Lee SE, Rabinovici GD, Mayo MC, et al. Clinicopathological correlations in
corticobasal degeneration. Ann Neurol. 2011; 70:327-340. [PubMed: 21823158]
12. Nutt JG. Higher-level gait disorders: an open frontier. Mov Disord. 2013; 28:1560-
1565. [PubMed: 24132844]
13. Dale ML, Curtze C, Nutt JG. Apraxia of gait- or apraxia of postural transitions?
Parkinsonism Relat Disord. 2018; 50:19-22. [PubMed: 29477458]

27/07/2018
Parkinsonian and Frontal

Lobe Gait Disorders
Simon Lewis
Professor of Cognitive Neuroscience
Royal Prince Alfred Hospital @profsimonlewis University of Sydney
Gait & Survival

• If the eyes are the windows on the soul
• Then the feet are the steps to the grave
1
27/07/2018
• Neurological disease
– Multiple levels of pathology
– Can be concomitant
• Cortex
• Striatum
• Brainstem
• Cord
• Peripheral (nerves, vestibular, muscle)
Locomotor pathways
2
27/07/2018
Bipedal Locomotion
• Highly complex
– Balance
– Movement
– Goal directed and automatic
• Integrated systems
– Multiple levels
• Complexity
– Second only to language
– Walk and TALK!
Bipedal locomotion
• Cortico-basal ganglia
– Voluntary and cognitive control processes
• Basal ganglia-brainstem system
– Automatic control of movement
• Muscle tone system and locomotor system
– Balance between net excitatory cortical input and
inhibitory basal ganglia input
• Sensory integration
– Proprioception/Visuomotor/Cerebellar/Vestibular
3
27/07/2018
Decerebrate locomotion
• MLR and PPN
– Activate the locomotor central pattern
generator (CPG) in the spinal cord
• Automatic processes
– Activation of basic motor programs
– Motor repertoires
4
27/07/2018
5
27/07/2018
Early PD
What is Early PD?
6
27/07/2018
Transition to Synucleinopathy
• Schenck et al1
– 29 older men with iRBD
– 10 year follow up
– 38% transitioned to parkinsonian disorder
(1) Schenck et al. (1996) Neurology
7
27/07/2018
• Iranzo et al 2013
– 14 year follow up period
• 36/44 participants (82%)
– Neurodegenerative syndrome
• Diagnosis
– 16 PD
– 14 LBD
– 1 MSA
– 5 MCI
Iranzo et al. (2013) Lancet Neurology
8
27/07/2018
Gait Abnormalities in iRBD

• Sleep regulating nuclei and regions
controlling gait and posture
– Extensive neuroanatomical connections
• Early regions for synucleinopathy
– Pontine tegmentum
– Pedunculopontine nucleus
– Medial medulla
• iRDB v Controls
– Decreased velocity and cadence
– Increased double limb support variability
– Greater stride/swing time variability
• No longitudinal follow up
– Relationship to transition remains unknown
9
27/07/2018
Gait Abnormalities in
Early and Incident PD
• Subjective complaints rare and often
compensated (faster shorter steps)
• Dual-tasking: “early (<5 y)”1
– ↑ stride width & number of cadences
– ↓ swing/cycle time
• Dual-tasking and Home Monitoring: “incident”
– Only ↑ step width variability on dual-tasking2
– Less active - inability to sustain levels of walking3
1 Panyakaew & Bhidayasiri. Journal of Neural Transmission 2013
2 Rochester et al. Neuroscience 2014. 3 Lord et al. J Neurol 2014
Gait Abnormalities in PD
• Nigrostriatal loss correlated with bradykinesia
– However, dopamine does not restore normal gait
• Motor phenotype
– No clear gait relationship differences between
PIGD and Tremor Dominant PD1
• Comorbid cortical cholinergic dennervation
– More robust marker of slowing of gait in PD than
nigrostriatal dennervation alone2
1 Herman et al. J Neurol 2014

2 Bohnen et al. Neurology 2014
10
27/07/2018
Advanced PD
Advanced PD
11
27/07/2018
Freezing of Gait
• Paroxysmal episodes of gait arrest
• Over 50% with advanced disease
• Limited therapeutic response
• Triggers/Relievers
– Turning
– Dual Tasking
– Doorways
– Cueing
Disease Stage
• H&Y Stage
Hall et al J Parkinsons Dis 2015
12
27/07/2018
Start Hesitation
Turn
13
27/07/2018
Turn
Dual Task
14
27/07/2018
Doorway
Cueing
15
27/07/2018
DLB parkinsonism
16
27/07/2018
DLB Grasp Reflex
DLB Palmomental Reflex
17
27/07/2018
DLB Luria
DLB Dyspraxia
18
27/07/2018
DLB Visuospatial
19
27/07/2018
MSA Gait
MSA
20
27/07/2018
Dysarthria
Eyes
21
27/07/2018
PSP Gait
22
27/07/2018
PSP Eyes
PSP Horizontal & Vertical
23
27/07/2018
PSP Grasp
PSP Dyspraxia
24
27/07/2018
PSP Applause Sign
25
27/07/2018
Pure Akinesia with Gait Freezing
26
27/07/2018
CBS Gait
27
27/07/2018
CBS
CBS Dyspraxia
28
27/07/2018
Marche à petits pas
29
27/07/2018
NPH
30
27/07/2018
Normal Pressure
Hydrocephalus
Normal Pressure
Hydrocephalus
• Shuffling Gait
– Parkinsonian
• Cognitive decline
– Frontal, dysexecutive
• Urinary Incontinence
31
27/07/2018
NPH pre- and post shunt
Video courtesy of Ben Jonker
Parkinson’s Gait Abnormalities

• Depends on Stage of Parkinson’s Disease
• “Early”
– Minimal difference (ageing, depression)
• “Mid”
– Asymmetry
– Lower stride length with velocity
compensation
• “Late”
– Falls & Freezing
32
27/07/2018
Gait Disorders
• Red flags
– Early falls
– Associated signs/symptoms (cognition, bladder)
• Upper limbs
– ‘In’ or ‘Out’
– Posture
• Additional signs
– Higher order
– Eye movements
33
27/07/2018
Parkinsonian and Frontal

Lobe Gait Disorders
Simon Lewis
Professor of Cognitive Neuroscience
Royal Prince Alfred Hospital @profsimonlewis University of Sydney
Gait & Survival

• If the eyes are the windows on the soul
• Then the feet are the steps to the grave
1
27/07/2018
• Neurological disease
– Multiple levels of pathology
– Can be concomitant
• Cortex
• Striatum
• Brainstem
• Cord
• Peripheral (nerves, vestibular, muscle)
Locomotor pathways
2
27/07/2018
Bipedal Locomotion
• Highly complex
– Balance
– Movement
– Goal directed and automatic
• Integrated systems
– Multiple levels
• Complexity
– Second only to language
– Walk and TALK!
Bipedal locomotion
• Cortico-basal ganglia
– Voluntary and cognitive control processes
• Basal ganglia-brainstem system
– Automatic control of movement
• Muscle tone system and locomotor system
– Balance between net excitatory cortical input and
inhibitory basal ganglia input
• Sensory integration
– Proprioception/Visuomotor/Cerebellar/Vestibular
3
27/07/2018
• MLR and PPN
– Activate the locomotor central pattern
generator (CPG) in the spinal cord
• Automatic processes
– Activation of basic motor programs
– Motor repertoires
4
27/07/2018
5
27/07/2018
Early PD
What is Early PD?
6
27/07/2018
• Schenck et al1
– 29 older men with iRBD
– 10 year follow up
– 38% transitioned to parkinsonian disorder
(1) Schenck et al. (1996) Neurology
7
27/07/2018
• Iranzo et al 2013
– 14 year follow up period
• 36/44 participants (82%)
– Neurodegenerative syndrome
• Diagnosis
– 16 PD
– 14 LBD
– 1 MSA
– 5 MCI
8
27/07/2018

• Sleep regulating nuclei and regions
controlling gait and posture
– Extensive neuroanatomical connections
• Early regions for synucleinopathy
– Pontine tegmentum
– Pedunculopontine nucleus
– Medial medulla
• iRDB v Controls
– Decreased velocity and cadence
– Increased double limb support variability
– Greater stride/swing time variability
• No longitudinal follow up
– Relationship to transition remains unknown
9
27/07/2018
Gait Abnormalities in
Early and Incident PD
• Subjective complaints rare and often
compensated (faster shorter steps)
• Dual-tasking: “early (<5 y)”1
– ↑ stride width & number of cadences
– ↓ swing/cycle time
• Dual-tasking and Home Monitoring: “incident”
– Only ↑ step width variability on dual-tasking2
– Less active - inability to sustain levels of walking3
1 Panyakaew & Bhidayasiri. Journal of Neural Transmission 2013
2 Rochester et al. Neuroscience 2014. 3 Lord et al. J Neurol 2014
Gait Abnormalities in PD
• Nigrostriatal loss correlated with bradykinesia
– However, dopamine does not restore normal gait
• Motor phenotype
– No clear gait relationship differences between
PIGD and Tremor Dominant PD1
• Comorbid cortical cholinergic dennervation
– More robust marker of slowing of gait in PD than
nigrostriatal dennervation alone2
1 Herman et al. J Neurol 2014

2 Bohnen et al. Neurology 2014
10
27/07/2018
Advanced PD
Advanced PD
11
27/07/2018
Freezing of Gait
• Paroxysmal episodes of gait arrest
• Over 50% with advanced disease
• Limited therapeutic response
• Triggers/Relievers
– Turning
– Dual Tasking
– Doorways
– Cueing
Disease Stage
• H&Y Stage
Hall et al J Parkinsons Dis 2015
12
27/07/2018
Start Hesitation
Turn
13
27/07/2018
Turn
Dual Task
14
27/07/2018
Doorway
Cueing
15
27/07/2018
DLB parkinsonism
16
27/07/2018
DLB Grasp Reflex
DLB Palmomental Reflex
17
27/07/2018
DLB Luria
DLB Dyspraxia
18
27/07/2018
DLB Visuospatial
19
27/07/2018
MSA Gait
MSA
20
27/07/2018
Dysarthria
Eyes
21
27/07/2018
PSP Gait
22
27/07/2018
PSP Eyes
PSP Horizontal & Vertical
23
27/07/2018
PSP Grasp
PSP Dyspraxia
24
27/07/2018
PSP Applause Sign
25
27/07/2018
26
27/07/2018
CBS Gait
27
27/07/2018
CBS
CBS Dyspraxia
28
27/07/2018
Marche à petits pas
29
27/07/2018
NPH
30
27/07/2018
Normal Pressure
Hydrocephalus
Normal Pressure
Hydrocephalus
• Shuffling Gait
– Parkinsonian
• Cognitive decline
– Frontal, dysexecutive
• Urinary Incontinence
31
27/07/2018
NPH pre- and post shunt
Video courtesy of Ben Jonker
Parkinson’s Gait Abnormalities

• Depends on Stage of Parkinson’s Disease
• “Early”
– Minimal difference (ageing, depression)
• “Mid”
– Asymmetry
– Lower stride length with velocity
compensation
• “Late”
– Falls & Freezing
32
27/07/2018
Gait Disorders
• Red flags
– Early falls
– Associated signs/symptoms (cognition, bladder)
• Upper limbs
– ‘In’ or ‘Out’
– Posture
• Additional signs
– Higher order
– Eye movements
33

Gait Problems in Parkinsonism and Frontal Lobe Gait Disorders - Original.1538514874

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Gait Problems in Parkinsonism and Frontal Lobe Gait Disorders - Original.1538514874

Uploaded by

Copyright:

Available Formats

The neuroanatomy of locomotion

Teaching Course 2309 1

The spectrum of gait disorder in Parkinson’s Disease

Parkinsonian and Frontal Lobe Gait Disorders

Teaching Course 2309 2

Higher level gait disorders (HLGD) are characterized by various combinations of

Teaching Course 2309 3

1. Takakusaki K, Tomita N, Yano M. Substrates for normal gait and pathophysiology of

Teaching Course 2309 4

Parkinsonian and Frontal

Royal Prince Alfred Hospital @profsimonlewis University of Sydney

Gait & Survival

Teaching Course 2309 5

Teaching Course 2309 6

Teaching Course 2309 7

Teaching Course 2309 8

Teaching Course 2309 9

What is Early PD?

Teaching Course 2309 10

(1) Schenck et al. (1996) Neurology

Teaching Course 2309 11

Iranzo et al. (2013) Lancet Neurology

Teaching Course 2309 12

Gait Abnormalities in iRBD

Gait Abnormalities in iRBD

Teaching Course 2309 13

1 Herman et al. J Neurol 2014

Teaching Course 2309 14

Teaching Course 2309 15

Hall et al J Parkinsons Dis 2015

Teaching Course 2309 16

Teaching Course 2309 17

Teaching Course 2309 18

Teaching Course 2309 19

Teaching Course 2309 20

DLB Grasp Reflex

DLB Palmomental Reflex

Teaching Course 2309 21

Teaching Course 2309 22

Teaching Course 2309 23

Teaching Course 2309 24

Teaching Course 2309 25

Teaching Course 2309 26

PSP Horizontal & Vertical

Teaching Course 2309 27

Teaching Course 2309 28

PSP Applause Sign

Teaching Course 2309 29

Pure Akinesia with Gait Freezing

Pure Akinesia with Gait Freezing

Teaching Course 2309 30

Teaching Course 2309 31

Teaching Course 2309 32

Marche à petits pas

Teaching Course 2309 33

Teaching Course 2309 34

Teaching Course 2309 35

NPH pre- and post shunt

Video courtesy of Ben Jonker

Parkinson’s Gait Abnormalities

Teaching Course 2309 36