Movement disorders and seizures
Movement and demyelinating disorders; seizures
These disorders each have a cell or pathway that fails: nigral dopamine neurons, oligodendrocyte myelin, motor neurons or an irritable piece of cortex. CPSP asks about the pathology and genetics of each and the signs on MRI, SPECT and CT that point to it.
Parkinson disease
- Loss of dopaminergic neurons in the substantia nigra pars compacta, with Lewy bodies (α-synuclein). Symptoms appear after much of the nigrostriatal supply is lost.
- Lewy pathology begins in the olfactory bulb and lower brainstem, so loss of smell and REM sleep behaviour disorder can precede the tremor by years.
- DaT SPECT shows reduced striatal uptake (putamen first) in Parkinson disease; it is normal in drug-induced parkinsonism (haloperidol) and essential tremor, because nerve terminals are intact.
- On high-resolution susceptibility MRI the normal 'swallow tail' (nigrosome-1) is lost.
- Treatment links: levodopa with carbidopa (peripheral decarboxylase inhibitor that does not cross the barrier).
Other movement disorders
| Disorder | Basis | Imaging |
|---|---|---|
| Huntington disease | Autosomal dominant CAG repeat (HTT, chromosome 4); anticipation, more with paternal transmission; each child 1 in 2 | Caudate atrophy, box-shaped frontal horns |
| Wilson disease | ATP7B, copper accumulation | Basal ganglia T2 change, 'face of the giant panda' in the midbrain |
| PKAN (iron accumulation) | Pantothenate kinase mutation | 'Eye of the tiger': dark globus pallidus with a bright centre |
| Hemiballismus | Contralateral subthalamic nucleus lesion (often lacunar stroke) | Small infarct |
Demyelination and nerve injury
- Multiple sclerosis: T-cell and antibody attack on CNS myelin made by oligodendrocytes; plaques are separated in space and time.
- MRI: ovoid lesions perpendicular to the ventricles (Dawson's fingers), plus juxtacortical, infratentorial and spinal lesions. Enhancement means active inflammation with barrier breakdown; an incomplete (open) ring favours demyelination over tumour or abscess.
- Oligoclonal IgG bands in CSF and not in serum show intrathecal synthesis by B-cell clones; not specific.
- Lhermitte sign (electric shock on neck flexion) means a cervical dorsal column lesion.
- ADEM: after a viral illness or vaccination, in children; large fluffy lesions, often thalami, all of the same age and monophasic.
- Metachromatic leukodystrophy: arylsulfatase A deficiency; symmetric periventricular white matter T2 change with a tigroid pattern, sparing the subcortical U-fibres.
- Neurapraxia (tourniquet, compression): focal demyelination with an intact axon; full recovery in weeks. Large myelinated motor and proprioceptive fibres are most vulnerable.
| Feature | Multiple sclerosis | ADEM |
|---|---|---|
| Course | Relapsing | Usually single episode |
| Lesions | Different ages; some enhance | Same age; enhance together |
| Grey matter | Rare | Thalami and basal ganglia often |
Motor neuron disease and polio
- Amyotrophic lateral sclerosis: mixed upper and lower motor neuron signs (wasting, fasciculation with brisk reflexes); sensation, eye movements and bladder are spared because oculomotor nuclei and Onuf's nucleus resist degeneration. MRI may show T2 bright corticospinal tracts in the posterior limb of the internal capsule.
- Poliomyelitis: virus destroys anterior horn cells; asymmetric flaccid paralysis with areflexia and normal sensation (unlike Guillain–Barré).
Seizures and epilepsy
- A seizure is synchronous neuronal discharge; focal seizures start in one region, generalised ones involve both hemispheres from the start.
- Absence seizures: 3 Hz spike-and-wave from thalamocortical circuits; ethosuximide blocks thalamic T-type calcium channels; carbamazepine can worsen absences.
| Cause | Typical patient | MRI or CT |
|---|---|---|
| Mesial temporal (hippocampal) sclerosis | Adult with focal seizures (epigastric rising, déjà vu, automatisms) and childhood febrile convulsions | Small hippocampus, T2/FLAIR bright, lost internal architecture |
| Focal cortical dysplasia | Drug-resistant childhood focal epilepsy | Thick cortex, blurred grey–white junction, transmantle sign |
| Tuberous sclerosis | Infantile spasms; loss of TSC1/TSC2 leaves mTOR overactive | Cortical tubers, calcified subependymal nodules, SEGA at the foramen of Monro (shrinks on everolimus) |
| Neurocysticercosis | Commonest cause of late-onset seizures in Pakistan | Cyst with scolex; dead cyst is a calcified dot without oedema |
| Rasmussen encephalitis | Child with progressive focal seizures and hemiparesis | Progressive atrophy of one hemisphere |
- After prolonged seizures, MRI may show cytotoxic oedema (restricted diffusion) in cortex and hippocampus that does not match an arterial territory and later resolves. Post-ictal weakness (Todd paresis) can mimic stroke.
Remember Parkinson disease is a loss of nigral terminals; if the DaT scan is normal, the terminals are there and the cause lies elsewhere.
Exam trap Oligoclonal bands support MS but are not specific; infections and other inflammatory diseases produce them too.
Exam trap Do not thrombolyse post-ictal Todd paresis mistaken for a stroke.
Test yourself on this topic
5 of the 19 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A 3-year-old girl who had walked normally now has a stiff, clumsy gait, absent ankle jerks and loss of speech. There is diffuse demyelination of the cerebral white matter and peripheral nerves, and urine sulfatides are raised. Deficiency of which enzyme is responsible?
Answer: Arylsulfatase A
Metachromatic leukodystrophy is an autosomal recessive lysosomal disorder caused by deficiency of arylsulfatase A. Sulfatides accumulate in oligodendrocytes and Schwann cells, which then fail to maintain myelin, so central and peripheral demyelination follow, explaining the spasticity with lost ankle jerks. The stored material stains metachromatically (brown with cresyl violet). Galactocerebrosidase deficiency causes Krabbe disease.
Metachromatic leukodystrophy
- Arylsulfatase A deficiency
- Sulfatides accumulate
- Central and peripheral demyelination
- Metachromatic staining
Remember Sulfatides in the white matter: arylsulfatase A is missing.
Exam trap Early sparing of U-fibres helps tell leukodystrophies from other white matter diseases.
Why the other options are wrong
- Galactocerebrosidase Causes Krabbe disease, with globoid cells and early infantile onset.
- Hexosaminidase A Causes Tay-Sachs disease, a grey matter storage disease with a cherry-red spot.
- Glucocerebrosidase Causes Gaucher disease.
- Alpha-galactosidase A Causes Fabry disease.
A 7-year-old has frequent brief staring spells with 3 Hz spike-and-wave discharges on EEG. The rhythmic thalamocortical firing behind these seizures depends mainly on which ion channel in thalamic relay neurons?
Answer: T-type calcium channels
Absence seizures arise from rhythmic oscillation between the thalamus and cortex. Thalamic relay neurons, when hyperpolarised, de-inactivate low-threshold T-type calcium channels; these then open and produce a burst of spikes, which recruits the cortex and, through the reticular nucleus, hyperpolarises the relay cells again. This cycle repeats about three times a second, giving the 3 Hz spike-and-wave. Ethosuximide works by blocking these T-type channels.
Absence seizures
- Thalamocortical 3 Hz rhythm
- Relay cells hyperpolarised
- T-type Ca2+ burst
- Blocked by ethosuximide
Remember Three-hertz staring spells come from thalamic T-type calcium bursts.
Exam trap Sodium channel blockers such as carbamazepine can make absences worse.
Why the other options are wrong
- Voltage-gated sodium channels Underlie ordinary action potentials; their blockers can worsen absences.
- GABA-A chloride channels Provide the inhibition that hyperpolarises relay cells, not the burst.
- NMDA glutamate receptors Not the driver of the thalamic burst.
- ATP-sensitive potassium channels Not the basis of the 3 Hz rhythm.
A 7-year-old girl has had increasingly frequent focal seizures of the left side of her body for two years, with continuous jerking of the left hand and a slowly worsening left hemiparesis. Biopsy of the right hemisphere shows T-cell infiltrates, microglial nodules and neuronal loss. What is the most likely diagnosis?
Answer: Rasmussen encephalitis
Rasmussen encephalitis is a rare chronic inflammatory disease of one cerebral hemisphere, mediated mainly by cytotoxic T cells, beginning in childhood. It causes drug-resistant focal seizures, often epilepsia partialis continua, and progressive hemiparesis and cognitive decline. The affected hemisphere progressively shrinks. Hemispherectomy or disconnection is often the only effective treatment.
Rasmussen encephalitis
- Chronic T-cell inflammation of one hemisphere
- Epilepsia partialis continua
- Progressive unilateral atrophy
- Treatment: hemispherectomy
Remember One hemisphere shrinking with relentless seizures: Rasmussen.
Exam trap A static perinatal infarct can cause similar signs; progression and active inflammation are the clues.
Why the other options are wrong
- Sturge-Weber syndrome Has a facial port-wine stain and pial angiomatosis.
- Hemimegalencephaly The affected hemisphere is enlarged and malformed from birth, without inflammation.
- Mesial temporal sclerosis Shows hippocampal neuronal loss and gliosis, not hemispheric inflammation.
- Perinatal MCA infarction A static perinatal lesion without active inflammation.
A 35-year-old farmer from Punjab has had occasional focal seizures for years. CT shows a single 3 mm dense calcified dot in the right frontal cortex with no surrounding oedema and no enhancement after contrast. What does this lesion represent?
Answer: Dead, calcified cysticercus
Neurocysticercosis passes through stages. The viable vesicular cyst is thin-walled with a scolex and little reaction. When the larva dies it enters the colloidal stage, with ring enhancement and oedema, which is the most symptomatic phase. It then shrinks (granular nodular stage) and finally calcifies, leaving a small dense dot without oedema or enhancement. Calcified lesions are a common cause of epilepsy in Pakistan and may still trigger seizures, but antiparasitic drugs have no role at this stage.
Neurocysticercosis stages
- Vesicular: cyst with scolex
- Colloidal: ring enhancement, oedema
- Granular nodular: shrinking
- Calcified: dense dot, dead larva
Remember A calcified dot is a dead cyst; no antiparasitic needed.
Exam trap Calcified cysts can still cause seizures, sometimes with intermittent perilesional oedema.
Why the other options are wrong
- Viable cyst with a visible scolex Appears as a CSF-density cyst with an eccentric dot, without calcification.
- Degenerating colloidal cyst Shows ring enhancement with surrounding oedema.
- Active tuberculoma with caseation Usually enhancing, often with oedema, and not a tiny calcified dot.
- Physiological choroid plexus calcification Lies in the ventricles, not in the frontal cortex.
A 29-year-old woman has had optic neuritis and, a year later, numbness of both legs. CSF electrophoresis shows several discrete IgG bands that are absent from her paired serum sample. What do these bands indicate?
Answer: Intrathecal IgG synthesis by B-cell clones
Oligoclonal bands are discrete bands of IgG produced by a limited number of plasma cell clones within the central nervous system. Bands present in the CSF but absent from serum prove intrathecal synthesis, and they are found in more than 90% of people with multiple sclerosis, supporting dissemination in time. Identical bands in CSF and serum ('mirror' pattern) reflect systemic production with passive leakage. A myeloma paraprotein gives a single band in both.
Oligoclonal bands
- IgG made within the CNS
- Bands in CSF, not serum
- Found in over 90% of MS
- Matched bands: systemic origin
Remember Bands only in the CSF mean the brain is making its own antibody.
Exam trap Oligoclonal bands are not specific; they also occur in CNS infections and other inflammatory diseases.
Why the other options are wrong
- Leakage of serum IgG across a damaged barrier Leaked serum IgG would show matching bands in serum.
- A monoclonal paraprotein from myeloma Would give a single monoclonal band in both serum and CSF.
- Bacterial antigens in the CSF Electrophoresis bands here are immunoglobulins, not bacterial antigens.
- Contamination of the sample with blood Blood contamination gives matched bands and red cells.
Where this sits in the CPSP syllabus
- Diagnostic Radiology, Paper 2: Nervous system disorders, Movement and demyelinating disorders; seizures