Neurology Flashcards
Clinical features of Parkisonism
Motor:
- Bradykinesia
- Tremor
- Rigidity
- Postural instability
- Masked face & monotone
- Striatal hand phenomenon
- Gait (shuffling gait, stooped posture, reduced arm swing)
- Micographia
Non-motor:
- sensory (pain)
- Autonomic - constipation
- Psychiatric: REM sleep behaviour disorder, excessive daytime sleepiness
Special test of PD
- Bradykinesia
- Gait
Parki-plus
- Vertical gaze (PSP)
- Cerebellar signs (MSA)
- BP
-MoCA
-Writing
-Drug history
Causes of Parkisonism
- Idiopathic Parkinson’s disease (80%)
- Parkinson-plus syndromes: MSA, PSP, CBD, DLB
- Vascular parkinsonism: lacunar infarcts at basal ganglia (characterized by lower body involvement)
- Drug-induced: dopamine antagonists (antipsychotics, antiemetics), valproate, methyldopa
- Metabolic disorders: Wilson’s disease, Huntington’s disease, anoxic brain damage post-cardiac arrest
- Toxins: CO, Mn, MPTP
- Infections: post-encephalitis, neurosyphilis, etc.
- Structural brain lesions: tumors of basal ganglia, normal pressure hydrocephalus, head trauma (Pugilist
Parkinson-plus syndromes differentiate from typical Parkinson’s disease
Red flags of atypical Parkinsonism:
o Early falls / postural instability
o Early dementia
o Bilateral symmetrical onset
o Early ANS dysfunction
o Poor response to L-DOPA
shorter survival, rapid progression, more frequent complications
What is Multiple system atrophy?
Clinical features, Subtypes, Radiological
Clinical features:
- Dysautonomia
- Cerebellar signs
- Pyramidal signs
Subtypes:
- MSA-P
- MSA-C
- Shy-Drager syndrome
Radiological:
- hot cross bun sign
What is Progressive supranuclear palsy?
Clinical features, Radiological sign
Clinical features:
- Axial rigidity —> hyperextended neck
- Vertical gaze palsy —> downward gaze
- Pseudobulbar palsy e.g. dysarthria, dysphagia
- Frontal signs: cognitive impairment, apathy, depression
Radiological sign:
- Hummingbird sign on sagittal MRI
- Mickey Mouse sign on transverse MRI
What is Corticobasal degeneration (CBD)?
Clinical features
Clinical features:
o Marked asymmetry (unlike other Parki-plus): clumsiness of one hand
o Cortical signs: limb apraxia, agnosia, alien limb phenomenon
o Dementia (late)
What is Dementia with Lewy bodies?
Clinical features
Diagnosis
Treatment
Clinical features:
- Dementia onset within 1 year
- Day-to-day cognitive fluctuations
- Visual hallucinations
- REM sleep behaviour disorder
Diagnosis:
- CT brain
Treatment:
- AChE inhibitors (Dementia)
- clozapine (Psychosis)
- levodopa-carbidopa (Parki)
- melatonin (RBD)
How to diagnose IPD?
Clinical diagnosis: Movement Disorder Society criteria
- Presence of Parkisonism
- more than 2 supportive criteria
- No red flag of atypical Parkinsonism
- Absence of absolute exclusion
if < 50 years old / other neurological signs (e.g. UMN) / suspect atypical Parki
• Imaging:
o MRI brain
o Dopamine transporter single-photon emission CT (SPECT): demonstrate loss of DA neurons, but cannot tell
PD from Parki-plus
• Others: TFT, B12/folate, VDRL, Wilson’s disease (ceruloplasmin, serum Cu, 24h urine Cu)
Management of IPD
Multidisciplinary team approach:
- exercise, speech therapy, screen depression, caregiver stress, fall prevention
Pharmacological therapy:
Start ALL patients on dopaminergic therapy
o MAO-B inhibitors: selegiline, rasagiline - neuroprotective effect
o If functional impairment (ADL, falls), add medications
—> Young (< 70) + good QoL: dopa-sparing drugs, e.g. dopamine agonist, anticholinergic
—> Old (>70) or poor QoL: levodopa combination (e.g. Sinemet, Madopar)
o Amantadine for dyskinesia
o SC Apomorphine for rescue
Surgical therapy:
- Deep brain stimulation: subthalamic nucleus (STN) or globus pallidus (GPi)
What is MAO-B inhibitor?
Can be used as monotherapy / combined with L-DOPA
• Potential neuroprotective effect
Example:
selegiline (available as patch),
rasagiline (more potent, less risk of cognitive S/E)
Side effects: insomnia, stomatitis, headache, serotonin syndrome (if +SSRI)
Levodopa use in IPD
Mechanism of action
Counselling for administration
Side effects
levodopa-carbidopa (Sinemet)
levodopa-benserazide (Madopar)
Mechanism of action:
- dopamine precursor
- combined with peripheral DOPA decarboxylase inhibitor to increase CNS bioavailability and reduce nausea
Counselling for administration:
- start at low dose with meals
- then take on empty stomach
- do not stop abruptly (Parkinsonism-hyperpyrexia syndrome)
- require multiple dosing (short half life)
Side effects:
- n/v —> increase dose of carbidopa and add domperidone
- Postural hypotension —> decrease anti-HT, give compression stockings, increase fludrocortisone, midodrine
- VH, delusion
- Motor fluctuation
o Types: wearing-off, delayed-on, no-on, random on-off
o Duration of benefit becomes shorter after long-term use
o Off phenomenon (end-of-dose akinesia):
—> Frequency / Switch to CR form
—> Add DA agonist/ COMT inhibitor/ MAOB inhibitor
—> SC apomorphine (short-acting DA agonist): rescue agent
o Peak-dose dyskinesia: choreiform in nature —> increase frequency, decrease dose, CR form —> Add amantadine (NMDA receptor antagonist) —> Offer DBS to young patients
What is DA agonist in IPD?
Type
S/E
Used to delay the use of L-DOPA
• Ergots (risk of restrictive valvular disease, retroperitoneal fibrosis): e.g. cabergoline
• Non-ergots (preferred): e.g. ropinirole / pramipexole PO, rotigotine daily patch
Side effects: similar to L-DOPA, but more non-motor side effects
• Impulse control disorders (activation of reward system)
o Risk factors: male, young, Hx/FHx of ICD / mood disorders
• Excessive daytime sleepiness
• Hallucinations
How is anti-cholinergics used in IPD?
Example: benzhexol/trihexyphenidyl (Artane)
Helpful for resting tremor-predominant PD
Side effects: dry mouth, constipation, AROU, glaucoma, cognitive decline —> caution in elderly
How is COMT inhibitor used in IPD?
Can only be used as adjunct to L-DOPA e.g. levodopa-carbidopa-entacapone (Stalevo)
Decrease GI metabolism of levodopa
might dyskinesia
Examples: entacapone, tolcapone
Side effects: brownish-orange urine discolouration, deranged LFT (tolcapone only)
Treatment for non-motor symptoms in IPD
• Depression: pramipexole / traditional antidepressants
• REM sleep behaviour disorder: clonazepam, melatonin
• Excessive daytime sleepiness: modafinil, methylphenidate
• Constipation: stool softeners, laxatives
Deep brain stimulation in IPD
Selection of patients:
o Idiopathic PD
o Advanced: > 5 years since diagnosis
o Excellent response to L-dopa (predict response to DBS)
o Motor fluctuations from L-dopa therapy (e.g. peak-dose dyskinesia) despite optimal treatment
o Age ≤ 75
o Severity: UPDRS motor score >30/108 at off state, Hoehn-and-Yahr grade ≥ 3
C/I:
o General: coagulopathy, medically unfit
o Specific: Parkinson-plus syndrome, mentally unfit (e.g MMSE < 24 / 30, comorbid psychiatric problem /
dementia)
Site of implantation:
- subthalamic nucleus
- globus pallidus interna
Procedure:
o Pre-operative: Madopar challenge test, MMSE, assessment by psychiatrist
Causes of syncope
- vasovagal - neurally related
—> associated with standing, emotion, situational (micturition), post exercise - orthostatic - postural related
—> related to plasma volume and drug (vasodilators), can be related to autonomic dysfunction or neurodegeneration - cardiac
—> arrhythmia related, tachycardia/ bradycardia, e.g. severe AS, HOCM, PE
Vasovagal syncope
Tiring (prodromal signs) —> syncope —> slow regain of consciousness (no neurological deficit but very tired)
Pathogenesis:
Trigger (emotional…) —> increase sympathetic system —> increase BP —> carotid body sense this —> activate parasympathetic system -> vasodilation + decrease HR —> but para > sym -> vasovagal syncope
VS cardiac cause, —> cardiac cause does not have prodromal signs
Syncope ddx
Neurogenic
- seizure, GTC
- ICH
-TIA
Vascular
-subcalvian steal syndrome
Metabolic
- hypoxia
-hypoglycaemia
Intoxication
Psychogenic
Definition and DDx of Spastic paraparesis
Definition: spasticity (velocity-dependent) + paraparesis (paralysis of both lower limbs)
DDx
1. Spinal cord
-Extrinsic cause
• Trauma
• Space occupying lesion
• Prolapsed disc / spondylosis
-Intrinsic causes
• Space occupying lesions
• Inflammation (transverse myelitis): MS, NMOSD,
ADEM, SLE
• Vascular: infarct (anterior spinal artery occlusion)
• Infection: TB, HSV, syphilis
• Iatrogenic: post-RT myelopathy
• Metabolic: B12 deficiency (subacute combined
degeneration of cord)
• Paraneoplastic
• Neurodegenerative: MND, Friedreich’s ataxia
• Hereditary: hereditary spastic paraparesis (usually AD)
- Brain stem
-Tumor - Cerebral
-cerebral palsy
-parasgaittal meningioma
Clinical feature of spastic paraparesis
Clinical features
• Initial phase may present as spinal shock (LMN: flaccid paralysis, areflexia, loss of sensation) for 1-2 weeks
• Recovery: hyperreflexia, return of anal tone & bulbocavernosus reflex
• Bilateral pyramidal signs
• Gait: scissoring gait, high steppage gait (UMN weakness of dorsiflexors), sensory ataxia
• Look for features of underlying causes
-Cord compression —> Sensory level (may be falsely localizing)
-Trauma —> scars/deformity
-MS —> Dorsal column sign, Cerebellar signs, eye signs
-B12 deficiency —> Peripheral neuropathy, upgoing plantar but absent ankle jerk, Anemia, jaundice, glossitis, splenomegaly
-Taboparesis(syphilis) —> Upgoing plantar but absent ankle jerk, Argyll-Robertson pupils
-Friedreich’s ataxia —> Cerebellar signs, pes cavus, kyphoscoliosis
-cervical myelopathy —> Lhermitte’ sign, myelopathy hand signs (e.g. inverted supinator jerk)
-Anterior spinal artery occlusion —> AF
What is Transverse myelitis?
Definition
Etiology
S/S
Ix
Mx
Definition: inflammation of spinal cord (without structural abnormalities, i.e. trauma / cord compression)
Aetiology
• Idiopathic
• Demyelinating disease (MC), e.g. MS, NMOSD, ADEM - i.e. TM as a precursor in MS spectrum
• Infection: HSV, enterovirus, syphilis
• Autoimmune: RA, SLE, AS, etc
• Paraneoplastic syndrome
S/S: severe neck/ back pain, subacute paraparesis with a sensory level
Investigations
• Demonstrate cord inflammation without compression:
o MRI spine with gadolinium contrast
o CSF: pleocytosis with elevated IgG
• Workup for underlying causes (e.g. B12, AQP-4, viral serology, malignancy screening, autoimmune panel)
Management
• IV methylprednisolone 1g daily for 7 days then taper dose —> if failed —> plasma exchange
• Treat underlying cause
• Consider prophylaxis if recurrent TM e.g. azathioprine
• Supportive care for complications, e.g. respiratory support, NG tube, analgesics, antispasmodic
What is cervical myelopathy?
Causes
Clinical features
Causes
• Cervical spondylosis (MC): degenerative disc, OPLL
• Trauma (whiplash injury)
• Tumor
• Inflammation: MS, NMOSD
• Infection: TB
Clinical features
• Motor: LMN at lesion level (fasciculations, wasting), UMN below lesion level
• Sensory: dermatomal pattern
• Pseudoathetosis: unconscious writhing movement of fingers with eyes closed (dorsal column damage)
• Lhermitte’s sign: shock-like sensation upon forced flexion of neck
• Myelopathic hand signs:
o Mid-cervical reflex pattern if C5-C7 affected: inverted biceps (biceps extends) & inverted supinator reflexes
(finger flexes), brisk triceps
o Finger escape test
o 10-second test / Grip and release test: should be able to open and close fist for ≥20 times
o Hoffman sign: flick DIP of middle finger à index and thumb will flex
Types of CNS demyelinations diseases
CNS inflammatory demyelinating diseases (IDD)
• MS
• NMOSD
• Myelin oligodendrocyte glycoprotein (MOG)-IgG+
disease: ADEM, ON, myelitis, etc
Definition, pathlogy and clinical patterns of multiple sclerosis
Definition:
chronic inflammatory demyelinating neurodegenerative disease in young adults, characterised by
multiple plaques of demyelination in CNS with dissemination in space & time
Pathology
• Epidemiology: 1/1000 in HK, female predominant
• Heterogenous and multifactorial:
o Genetics: HLA-DRB1 gene
o Environment: reduced vitamin D/ sun exposure, virus (EBV, HHV-6)
• Disrupted blood brain barrier à autoreactive T cell + B cell infiltration à microglia and astrocyte activation à
white + grey matter demyelination (cortical lesions, brain atrophy)
Clinical patterns
• Relapsing remitting (RRMS): MC (85%); 75% go into SPMS
• Primary progressive (PPMS)
• Secondary progressive (SPMS): often pyramidal weakness + cerebellar signs
• Progressive relapsing (PRMS)
Clinical features of multiple sclerosis
Clinical features
4 areas: sensory + cerebellar + UMN + optic
• Patchy neurological deficits in any part of CNS, with predilection at
o Optic nerve (1/3):
§ Optic neuritis: ¯VA, ¯colour vision, unilateral eye pain, optic atrophy on fundoscopy, RAPD +ve
o Brainstem (1/3):
§ Gaze palsies: Bilateral INO, conjugate horizontal gaze palsy, one-and-a-half syndrome
§ Bulbar S/S: dysarthria, dysphagia
§ Facial weakness (UMN type)
o Spinal cord (1/3):
§ Spastic paraparesis esp. LL, pyramidal signs (corticospinal tract)
§ Loss of proprioception & vibration, sensory ataxia with Romberg’s test +ve (DCML)
§ Paresthesia / hypesthesia (STT)
§ Lhermitte’s sign, myelopathic hand signs (e.g. pseudoathetosis)
o Cerebellar signs: ataxia, dysmetria, dysdiadochokinesia
o Autonomic neuropathy:
§ Bladder dysfunction (>90%): urgency (MC), frequency, retention of urine
§ Bowel dysfunction (e.g. constipation), sexual dysfunction
• Uhthoff’s phenomenon: symptoms worse in heat (heat-induced conduction blockade)
How to investigate and diagnose multiple sclerosis?
Diagnosis: revised McDonald criteria (2017)
Three components: DIT + DIS + exclude alternate DDx
• Dissemination in time (DIT) can be demonstrated by any one of:
o ≥ 2 clinical attacks
o New T2-hyperintense / gadolinium-enhancing lesions on follow-up MRI (irrespective of timing of baseline
MRI)
o Simultaneous presence of gadolinium-enhancing and non-enhancing lesions at any time
o CSF oligoclonal bands (intrathecal IgG production)
• Dissemination in space (DIS) can be demonstrated by:
o T2-hypertense lesions in ≥2 of the 4 CNS regions (periventricular, cortical/juxtacortical, infratentorial,
spinal cord)
• Exclude alternative diagnosis
*New additions in 2017 criteria
Investigations
• MRI brain + whole spine with gadolinium contrast
o Old plaques: T2/FLAIR-hyperintense, T1-iso/hypointense (“T1 black
holes”)
o New plaques: T2/FLAIR-hyperintense, gadolinium-enhancing (marker of active disease: BBB breakdown —> leakage of Gd)
Dawson fingers
o Neurodegeneration: brain atrophy of both gray matter and white matter with volume loss > 0.4%/year
• CSF (not routine): oligoclonal bands with intrathecal IgG
• Antibodies: anti-AQP4, anti-MOG
Management of multiple sclerosis
• Treatment goal: achieve NEDA (No Evidence of Disease Activity) – 4 parameters!
o Clinical: no confirmed relapses, no sustained disability progression (EDSS: Expanded Disability Standard Scale)
o Imaging (MRI = best biomarker): no new/enlarging T2 lesions, no annual brain volume loss (BVL) >0.4%
• Management of acute MS flare
o IV high-dose methylprednisolone (1g daily x 3-7 days)
§ Then short term (2 weeks) tapering oral prednisolone (e.g. 40mg à 30mg à 20mg à 10mg)
o Severe: may require plasma exchange or IVIG 0.4mg/kg/day x 5 days
• Disease modifying therapy (DMT)
o Approaches: escalation (most patients) vs induction (for multiple/disabling relapses or extensive MRI)
o First line:
- IFNb 1a/1b: IM injection, S/E: flu-like illness (myalgia, fatigue, fever), injection site reaction
- Teriflunomide (Aubagio): PO QD, C/I in pregnancy, S/E: headache, n/v/d, alopecia
- Dimethyl fumarate (Tecfidera): PO BD, S/E: flushing, abdo pain, n/v/d
o Second line (more potent, but more S/E): SFI
- Fingolimod (PO): first-line for induction approach in highly active patients, S/E: n/v/d, headache
- Natalizumab: IV monthly, risk of PML (note)
- Alemtuzumab
o Rituximab: for refractory MS / overlap with NMOSD
o Potential role: autologous HSCT, cladribine, siponimod, ocrelizumab, ofatumumab
• Offer annual MRI monitoring for new/enlarging and enhancing lesions
• Symptomatic treatment
o Spasticity: baclofen, benzodiazepines, Botox, splinting
o Urinary retention: anticholinergic, self-catheterisation
o Sexual dysfunction: PDE5 inhibitors
o Fatigue: methylphenidate
o Weakness, ataxia, gait disturbance: PT, OT, walking aids
o Dysarthria, dysphagia: ST
MS in pregnancy
• Pre-conception counselling: avoid pregnancy until MS activity is quiescent for 1 year
• Teratogenicity of certain DMT (e.g. teriflunomide, fingolimod): consider drug holiday if stable condition
o Teriflunomide: prescribe oral cholestyramine / activated charcoal for active elimination
• Interferons and natalizumab are safe
• Relapse rate reduces during pregnancy
• Risk of post-partum flare up: DMT can be resumed immediately postpartum
Progressive multifocal leukoencephalopathy (PML)
• Severe CNS demyelinating disease due to reactivation of JC virus (John Cunningham virus)
• Risk factors: immunocompromised (HIV, use of natalizumab / rituximab)
• S/S: altered MS, motor deficit, sensory deficit, etc
Neuromyelitis optica spectrum disorder (NMOSD)
• Pathology: demyelination + axonal degeneration (c.f. MS)
• Predilection of plaques at optic nerve + spinal cord ≥ 3 consecutive spinal segments
IPND diagnostic criteria for NMOSD (2015)
Stratified according to AQP4 status
• AQP4-IgG +ve: at least 1 core clinical characteristics
• AQP4-IgG -ve: at least 2 different core clinical characteristics (i.e. recurrent ON / recurrent TM alone insufficient),
with at least 1 of bolded ones, plus supporting features on MRI
Core clinical characteristics: optic neuritis (ON), acute myelitis with LETM, area postrema syndrome (APS), acute
brainstem syndrome, symptomatic narcolepsy + typical diencephalic lesions, symptomatic cerebral signs + typical brain lesions
NMO
- Age of onset: Late 30s - 50
- M:F 1:9
- Race: Asians
S/S
Less recovery, more relapses (>90%)
• Optic nerve: usually bilateral optic neuritis
• Lower brainstem: area postrema syndrome (intractable
hiccups, n/v), no INO
• Spinal cord: Longitudinal extensive transverse myelitis
(LETM) (e.g. symmetrical paraparesis, sensory level,
autonomic failure)
- Serology: Anti-aquaporin-4 (anti-AQP4 / NMO-IgG) (60%)
(AQP-4: water channel at foot of astrocytes) - Pleocytosis (↑WBC)
No oligoclonal bands - MRI Brain:
Brain: atypical changes (50%), brainstem lesions (15%)
Spinal cord: affect ≥3 consecutive spinal segments (LETM) - Acute treatment: Steroid, plasma exchange, IVIG (for NMOSD)
- Long-term immunosuppressant:
Treat for at least 5 years if seropositive (AQP4 +ve) - Prednisolone, azathioprine, MMF, rituximab
Others: eculizumab (C5 inhibitor), satralizumab (anti-IL6),
inebilizumab (anti-CD19)
Avoid MS-specific DMT: e.g. IFN/ fingolimod/ natalizumab
Acute disseminated encephalomyelitis (ADEM)
• Multifocal monophasic demyelinating disease seen after viral infection (esp. measles, VZV) or vaccination
• S/S: meningism, encephalopathy (confusion, memory impairment), seizures
• CT/MRI: small homogenous lesions (i.e. no dissemination in time & space)
• CSF: rule out meningitis/encephalitis, +/- increased protein and lymphocytosis
• Mx: IV high-dose methylprednisolone +/- IVIG / plasmapheresis
Anti-NMDA receptor encephalitis
Clinical features:
Young female, associated with ovarian teratoma (paraneoplastic syndrome)
• Neuropsychiatric symptoms
• Memory deficits & Movement disorders
• Decreased GC and catatonia & Language dysfunction
• Autonomic dysfunction
• Seizure + Sleep disturbances
Investigations:
• Serum & CSF Ab panel: CSF anti-NMDAR titre correlates with clinical outcome and is more sensitive
o CSF may also show lymphocytic pleocytosis / oligoclonal bands +ve
• Brain MRI (50% sensitivity): transient FLAIR / contrast-enhancing abnormalities in cortical / subcortical regions
Management:
• Treat underlying malignancy if any
• IVIG + IV methylprednisolone
• Alternatives: plasma exchange, cyclophosphamide, rituximab
Prognosis
Poor prognostic factors include: not associated with malignancy, did not receive immunosuppression during 1st attack
Etiology Cerebellar syndromes
Unilateral:
• vascular: Cerebellar stroke (ischemic/haemorrhage)
• Neoplastic: cerebellopontine angle tumour
Bilateral:
• Drugs and toxins: anti-epileptics (e.g. phenytoin), lithium, chemotherapy (e.g. 5-
FU), alcohol intoxication
• Metabolic: chronic alcoholism, Wernicke’s encephalopathy, hypothyroidism
• Autoimmune: multiple sclerosis, Miller-Fisher syndrome, SLE
• Paraneoplastic: anti-Yo (gynae / breast), anti-Hu (SCLC, prostate)
• Neurodegenerative: MSA, PSP
• Hereditary: Wilson’s disease (AR), spinocerebellar ataxia (AD), Friedreich’s ataxia
(AR), ataxia-telangiectasia (AR)
• Infection: viral/TB meningitis
Clinical features of Cerebellar syndromes
Ipsilateral lesion
Midline lesion: ocular and balance abnormalities
• eye signs: gaze-evoked nystagmus, broken pursuit, hypermetric saccades
• Truncal ataxia: wide-based gait. Worsened on tandem walking, Romberg’s test -ve
Hemispheric lesion: limb abnormalities
- Dysmetria: past-pointing
- Dysdiadochokinesia
- Intension tremor
- Scanning dysarthria
- Pronation drift and rebound test +ve
- Pendular knee jerk
Hereditary ataxias
Spinocerebellar ataxia
• Genetics: trinucleotide repeat expansion (CAG)
• Most common subtype in Asia: Type 3 (AD)
o Characterized by ataxia, pyramidal signs (UMN), extra-pyramidal signs (Parkinsonism), ophthalmoplegia
• Investigations: genetic testing, electrophysiology, neuroimaging
Friedreich’s ataxia
• Genetics: trinucleotide repeat expansion (GAA) à loss-of-function mutation in frataxin gene (Chr 9q13)
o Inheritance: AR
o Severity depends on number of expansions: earlier onset & loss of ambulation, more cardiomyopathy
• Clinical features:
o Pes cavus, inverted foot, hammer toes (long-standing peripheral neuropathy ~CMT)
o Limb ataxia: cerebellar & sensory ataxia
o Cerebellar eye signs: gaze-evoked nystagmus, broken pursuit, hypermetric saccades
o Kyphoscoliosis
o Associations: diabetes, hypertrophic cardiomyopathy (MC cause of death: heart failure), optic atrophy,
sensorineural hearing loss, high-arched palate
Ataxia-telangiectasia
• Genetics: ATM gene (Chr 11), AR inheritance
• Clinical features:
o Immunodeficiency: bronchiectasis
o Telangiectasias
o Increased risk of lymphoma/leukemia
Etiology, Clinical features, Diagnosis and management of Amyotrophc lateral sclerosis
Most common form of progressive MND
Amyotrophic (LMN denervation of anterior horn cells) + lateral sclerosis (UMN lesion
of corticospinal tracts)
Etiology
• 90% sporadic
• 10% familial: AD mutations in c9orf72 / SOD1
• Pathophysiology: excitotoxicity hypothesis, free radical hypothesis
Clinical features
• Mixed UMN and LMN signs (both corticospinal and bulbar)
• NO sensory signs / autonomic dysfunction / cognitive impairments
Bulbar:
- UMN:
Spastic dysarthria
Exaggeration of motor expression of
emotions (“pseudobulbar affect”)
Laryngospasm
- LMN:
Difficulty in chewing
Dysphagia
Difficulty in movement of face and tongue
Tongue fasciculations
Limbs:
- UMN:
Stiffness out of proportion to weakness
Hyperreflexia, spasticity, myoclonic jerk
- LMN:
Hyporeflexia, fasciculation
Foot drop
Diagnosis
World Federation of Neurology criteria / El Escorial criteria
• Simultaneous UMN and LMN involvement in 4 areas (bulbar, cervical, thoracic, lumbosacral)
o Definite ALS: 3 out of 4 involved
• Exclude all alternate diagnoses
Management
Multidisciplinary team approach
• Symptomatic treatment
o Drooling: anticholinergics (e.g. hyoscine patch)
o Dysphagia: ST / dietician, food thickeners, tube feeding
o Fasciculations: vit E supplement
o Spasticity / weakness: PT, OT (splint, neck support), baclofen
o Respiratory: NIV
• Disease-modifying treatment: riluzole (glutamate release inhibitor: reduce excitatory neurotoxicity)
o S/E: n/v/d, dLFT
Other forms of MND
• Progressive muscular atrophy (LMN)
• Primary lateral sclerosis (UMN)
• Progressive bulbar palsy (bulbar)
• ALS-plus syndromes (e.g. ALS+FTD)
