Degenerative Conditions

Parkinson’s disease

This is a disease where the dopaminergic neurons in the substantia nigra are progressively lost, resulting in the development of symptoms.

Parkinsonism can be drug-induced (gives rapid-onset bilateral motor symptoms)

Symptoms

Tremor, described as a pill-rolling motion of thumb over fingers, which is usually worse at rest and typically improves with movement

Bradykinesia – slow initiation of voluntary movements

Hypertonia – increased muscle tone, which gives cogwheel rigidity in the extremities

Postural instability and shuffling/festinant gait (pitched forward gait)

Expressionless face (“mask-like”)

Psychiatric – depression (most common symptom), dementia and psychosis

Micrographia, anosmia

Autonomic dysfunction (postural hypotension and constipation)

Key tests

It is a clinical diagnosis. SPECT (DaT scan) shows reduced dopaminergic activity in basal ganglia

Management

1st line is levodopa (often combined with dopa decarboxylase inhibitor, e.g., carbidopa, dopamine agonist (such as rotigotine) or MAO-inhibitor (such as selegiline)

2nd line is dual therapy or COMT inhibitor (entacapone)

Multiple Sclerosis

This is an autoimmune disorder against the CNS oligodendrocytes which produce myelin, which eventually leads to axonal loss.

It is the commonest cause of chronic neurological disability in young adults.

All sub-types, except for primary progressive, have a female preponderance.

Risk factors

Family history

Low vitamin D

Smoking

HLA-DR2 serotype

Living away from the equator

Infectious mononucleosis

Female gender

Symptoms

Presents with relapsing neurological deficits with periods of remission

Vision – optic neuritis, saccadic movements, desaturation of red-green colour vision

Sensory – asymmetrical pins and needles, trigeminal neuralgia

Motor – UMN symptoms, e.g., spasticity, muscle weakness

Cerebellar – ataxia, tremor

Cognitive – “brain fog”, memory impairment, executive dysfunction

Autonomic dysfunction – incontinence, sexual dysfunction, and fatigue

To be diagnosed, there must be “dissemination in time and space”.

This means that there must be more than one episode affecting more than one part of the nervous system.

Key tests

MRI – this is used to exclude other causes; contrast enhancement shows active disease, whereas lesions that don’t enhance are older lesions, known as plaques.

Lumbar puncture – shows IgG (oligoclonal bands) and myelin basic protein in CSF

CSF oligoclonal bands shows CNS inflammation and, if they’re not present in a concurrent serum sample, then it supports diagnosis of MS.

Management

Address symptoms accordingly – e.g., baclofen can be used for spasticity

Acute flare – high-dose steroids for 3–5 days (shorten length of relapse)

Chronic – disease modifying therapies reduce relapse frequency, e.g., β-interferon, fingolimod, and monoclonal antibodies, e.g., natalizumab (mAb against α4-integrin)

Huntington disease

This is an autosomal dominant disorder caused by trinucleotide repeats (CAG) in the huntingtin gene, leading to the formation of abnormal huntingtin protein.

The disease affects the caudate nucleus of basal ganglia initially, and then causes progressive loss of neurons in other brain regions.

It results in weak inhibition from the indirect pathway of the basal ganglia, allowing unnecessary movements.

This leads to excessive uncontrolled movements, which is characteristic of the disease (although not specific) usually starting around age 35–45.

Symptoms

Irritability and incoordination

Chorea (uncontrolled, hyperkinetic movements)

Behavioural problems, depression and progression to dementia

Management

Supportive management, including tetrabenazine, benzodiazepines and antipsychotics as there is no cure available

Spongiform encephalopathy

This is a group of rare degenerative diseases, caused by abnormal prion proteins in the brain, leading to misfolded normal proteins and subsequent brain damage (including formation of holes in the brain, thus causing its “spongiform” appearance).

Creutzfeldt-Jakob disease (CJD)

The most common spongiform encephalopathy, which usually occurs sporadically.

Variant CJD

This is a form seen in younger patients (average age is 25 years). It can very rarely be transmitted through dietary intake and gives anxiety and withdrawal early.

Symptoms

Rapidly progressive dementia

Myoclonus (spasmodic, jerky contraction of groups of muscles)

Can have ataxia (cerebellum involvement) and eye signs (diplopia, field defects

Key tests

Lumbar puncture – CSF shows presence of 14-3-3 protein; RT-QuIC assay can be used to break prion aggregates, which then can replicate sufficiently to be measured

EEG shows biphasic sharp waves

MRI shows hyperintensity in basal ganglia and thalamus

Definitive diagnosis is only available at post-mortem

Management

No treatment available and the condition usually has a poor prognosis