5.3 Movement Disorders, Dementia & Peripheral Neuropathies
Key Takeaways
- Parkinson disease presents with asymmetric resting tremor (4-6 Hz pill-rolling), rigidity, and bradykinesia, caused by loss of dopaminergic neurons in the substantia nigra pars compacta with alpha-synuclein Lewy bodies.
- Essential tremor is an 8-12 Hz action/postural tremor that improves with alcohol ingestion and responds to first-line treatment with propranolol or primidone.
- Alzheimer disease accounts for 60-80% of dementia cases, characterized by short-term memory loss, temporal lobe atrophy, amyloid-beta plaques, and hyperphosphorylated tau neurofibrillary tangles.
- Guillain-Barré syndrome presents as acute ascending flaccid paralysis with areflexia following Campylobacter jejuni infection, showing CSF albuminocytologic dissociation (high protein, normal cell count).
- Normal Pressure Hydrocephalus presents with gait apraxia, urinary incontinence, and cognitive decline ('wobbly, wet, and wacky'), treated definitively with a ventriculoperitoneal (VP) shunt.
Extrapyramidal Movement Disorders
Extrapyramidal movement disorders stem from dysfunction within the basal ganglia circuitry, manifesting as hyperkinetic or hypokinetic motor syndromes.
Tremor Differential Diagnosis
Differentiating tremor syndromes relies on evaluating tremor frequency, baseline activation state (resting vs. postural/action vs. kinetic), and responsiveness to alcohol or pharmacotherapy:
| Tremor Type | Frequency & Activation | Associated Features | First-Line Pharmacotherapy |
|---|---|---|---|
| Parkinsonian Tremor | 4 to 6 Hz resting tremor ("pill-rolling"); decreases with voluntary action | Asymmetric onset; accompanied by bradykinesia, cogwheel rigidity, and postural instability | Levodopa / Carbidopa; Pramipexole; Trihexyphenidyl (young patients) |
| Essential Tremor | 8 to 12 Hz postural / action tremor; absent at rest | Bilateral, symmetric hands/arms/head involvement; attenuated by alcohol; strong family history | Propranolol (non-selective beta-blocker) or Primidone |
| Cerebellar Tremor | <5 Hz kinetic / intention tremor; worsens as hand approaches target | Ipsilateral dysmetria, dysdiadochokinesia, and gait ataxia | Treat underlying etiology (e.g., multiple sclerosis, stroke, alcohol abuse) |
Parkinson Disease & Related Parkinsonism
Parkinson disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra pars compacta.
- Neuropathology: Intracellular inclusions containing aggregated alpha-synuclein (Lewy bodies).
- Cardinal Manifestations (TRAP Mnemonic):
- Tremor: 4–6 Hz resting tremor
- Rigidity: Cogwheel or lead-pipe resistance to passive joint motion
- Akinesia / Bradykinesia: Slowness of movement, micrographic handwriting, mask-like facies, decreased arm swing while walking
- Postural Instability: Impaired righting reflexes leading to frequent falls (typically late stage)
- Pharmacotherapy: Levodopa combined with carbidopa (peripheral dopa-decarboxylase inhibitor preventing peripheral conversion to dopamine and reducing nausea). Dopamine agonists (pramipexole, ropinirole) are used as initial monotherapy in younger patients (<60 years) to delay levodopa-related motor fluctuations (dyskinesias).
Cognitive Impairment & Dementia Syndromes
Dementia is defined as major neurocognitive decline that interferes with independent daily functioning.
[ Clinical Dementia Presentation ]
|
(History, Neuropsychological Testing, MRI)
|
+-------------------+---------------------+--------------------+--------------------+
| | | | |
[ Alzheimer Disease ] [ Vascular Dementia ] [ Lewy Body Dementia ] [ Frontotemporal ] [ NPH ]
| | | | |
(Insidious memory (Stepwise decline, (Visual hallucinations, (Personality change, (Gait apraxia,
loss, amyloid/tau, infarcts on MRI, parkinsonism, REM disinhibition, incontinence,
temporal atrophy) executive loss) sleep disorder) tau/TDP-43 bodies) VP shunt tx)
Comprehensive Comparison of Major Dementia Syndromes
- Alzheimer Disease (AD): Accounts for 60–80% of cases. Characterized by insidious onset of short-term memory impairment, spatial disorientation, and anomia. MRI demonstrates prominent hippocampal and temporal lobe atrophy. Histology reveals extracellular amyloid-beta plaques and intracellular hyperphosphorylated tau neurofibrillary tangles. Treatment includes cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and NMDA receptor antagonists (memantine).
- Vascular Dementia: Characterized by a stepwise cognitive decline coinciding with focal ischemic strokes or cumulative subcortical white matter microvascular disease. Early executive dysfunction predominates. Brain MRI reveals multi-infarct lesions or diffuse leukoaraiosis. Prevention involves aggressive vascular risk factor control.
- Dementia with Lewy Bodies (DLB): Characterized by the clinical triad of detailed visual hallucinations, fluctuating cognitive impairment, and spontaneous parkinsonism. Patients demonstrate severe neuroleptic sensitivity (extreme adverse reactions to typical antipsychotics) and REM sleep behavior disorder. Cortical Lewy bodies are present on pathology.
- Frontotemporal Dementia (Behavioral Variant FTD / Pick Disease): Onset typically occurs at a younger age (50–65 years). Characterized by early personality changes, disinhibition, apathy, loss of empathy, and hyperorality, with relative preservation of memory and visuospatial skills. Brain MRI reveals focal frontal and anterior temporal lobe atrophy.
- Normal Pressure Hydrocephalus (NPH): Reversible cause of cognitive decline caused by impaired CSF resorption. Classic clinical triad: Gait apraxia ("magnetic gait", feet stuck to floor) → Urinary incontinence → Dementia ("wobbly, wet, and wacky"). Brain imaging shows ventriculomegaly disproportionate to cortical sulcal atrophy. Diagnosis is supported by a large-volume lumbar puncture (tap test) showing gait improvement; treatment is surgical placement of a ventriculoperitoneal (VP) shunt.
Peripheral Neuropathies & Neuromuscular Disorders
Guillain-Barré Syndrome (GBS)
Guillain-Barré syndrome is an acute, immune-mediated polyradiculoneuropathy characterized by progressive symmetric ascending flaccid paralysis and hyporeflexia/areflexia.
- Trigger: Cross-reactive antibodies (molecular mimicry) following gastrointestinal infection with Campylobacter jejuni or respiratory viral illnesses.
- Diagnostic Findings: Lumbar puncture demonstrates albuminocytologic dissociation (elevated CSF protein >45 mg/dL with a normal CSF white blood cell count <10/mm³). Electrodiagnostic studies show nerve conduction slowing and demyelination.
- Respiratory & Autonomic Monitoring: Serial monitoring of Forced Vital Capacity (FVC) and Negative Inspiratory Force (NIF) is essential. An FVC <20 mL/kg or NIF < -30 cmH₂O indicates impending respiratory failure requiring elective mechanical ventilation.
- Treatment: Intravenous Immunoglobulin (IVIG) or Plasmapheresis (Plasma Exchange). Corticosteroids are ineffective and contra-indicated in GBS.
Amyotrophic Lateral Sclerosis (ALS)
ALS is a fatal neurodegenerative disease involving both upper motor neurons (UMN) and lower motor neurons (LMN).
- Clinical Signs: Combined UMN signs (spasticity, hyperreflexia, positive Babinski sign) and LMN signs (muscle atrophy, fasciculations, flaccid weakness) in multiple spinal/bulbar segments without sensory deficits.
- Disease-Modifying Therapy: Riluzole (glutamate neurotransmission inhibitor, extends survival by 2–3 months) and Edaravone (free radical scavenger).
A 64-year-old male presents with a 9-month history of bilateral hand tremor. The tremor occurs when he reaches for a glass of water, writes, or holds a newspaper, but disappears completely when his hands are fully supported at rest. He notes that drinking a glass of wine significantly attenuates the tremor. His father had a similar tremor. Neurological examination reveals a 9 Hz kinetic tremor without rigidity or bradykinesia. What is the first-line medication for this condition?
A 32-year-old male is evaluated in the emergency department for progressive weakness in both legs that began 3 days ago and has now spread to involve his upper extremities. Two weeks ago, he recovered from a self-limited diarrheal illness. Physical examination reveals bilateral symmetric lower extremity weakness (3/5 strength) and absent patellar and Achilles deep tendon reflexes. A lumbar puncture is performed. Which cerebrospinal fluid (CSF) profile is most characteristic of this patient's underlying condition?
A 76-year-old male is brought to the outpatient neurology clinic by his daughter due to progressive walking difficulties over the past 6 months. She describes his gait as slow, shuffling, and looking as though his feet are 'glued to the floor.' Over the past 3 months, he has developed urinary urgency and involuntary nighttime incontinence. His daughter has also noticed mild memory impairment and slowness of thought. A non-contrast head CT demonstrates symmetrical ventricular enlargement out of proportion to cortical sulcal atrophy. What is the definitive treatment for this patient's condition?