MND Flashcards
Poor prognostic factors
At time of presentation:
- Bulbar onset
- Respiratory involvement including reduced FVC
- Rapid progression of symptoms
- Weight loss
- Older age
- Low ALSFRS-R
- Certain gene mutations
MND diagnostic criteria
- el escorial
- gold coast
-
“MND protocol”
Bloods:
- Haem/ Biochemistry, B12/folate, Vit D, ESR
- CK (beware only slight elevation in IBM, and also in MND)
- TFTs
- Antibodies e.g. AChR, Anti-GM1
- Oligoclonal bands
- ?VLCFA
Consider genetic testing:
- C9/SOD1, etc.
- HSP gene
- SMA gene
- Kennedy’s disease
LP:
- Oligoclonal bands
- Cell counts, protein, glucose
-
Neuroimaging:
- MRI Brain / Spine
Neurophysiology:
- EMG and NCS
(may do single fibre/ repetitive EMG for ?MG)
- Might also do EMG with TMS to observe for cortical hyperexcitability
Things to cover in clinic review
a) Symptoms
b) Holistic
c) Services involved
d) Medications
a) Limbs:
- Muscle weakness, mobility, cramps, spasticity, fatigue, pain
- ADLs
Bulbar:
- Swallowing, eating, weight, speaking (voice banking), saliva
Respiratory:
- Dyspnoea, orthopnoea, sleep, daytime sleepiness, morning headaches
Psych:
- Cognitive disturbance
- Behavioural disturbance
- Emotional lability
- Depression/anxiety
- ADLs
b) - Check understanding of MND, progression, etc.
- Advance care planning, including DNACPR, ADRT, LPA, views about NIV/PEG
- DVLA
- Life insurance/pensions, etc.
- Family support/carer support
c) Physical:
- Physio/OT
- orthotics (e.g. foot-up device, head-up collar)
- Wheelchair services
Nutrition:
- Dietitian/SALT/AAC/ voice bank
- PEG referral
Respiratory:
- Physiology
- NIV
Social:
- Social services
- Counselling
- Palliative care
d) - Riluzole - started, tolerated, monitored
Cramps:
- 1st - quinine 200mg-300mg ON
- 2nd - baclofen 5-10mg TDS
- 3rd - tizanidine, dantrolene, gabapentin
Spasticity:
- Baclofen, tizanidine, dantrolene, gabapentin
Sialorrhoea*:
- Thick - rehydrate, medication review (reduce anticholinergics), carbocisteine, suctioning, SALT
- Thin - anticholinergics (hyoscine patch, glycopyrronium SC/PO/PEG, atropine eye drops sublingually, amitriptyline), Botox (only if already has PEG), radiotherapy, SALT
*https://pn.bmj.com/content/17/2/96
Respiratory insufficiency in MND
a) Test results
b) Referral if in T2RF
a) FVC <50% pred, or <80% pred if symptomatic
b) Within 1 week
Facts and figures
a) Number living with MND in UK at any one time
b) Lifetime risk of MND
c) % family history
d) % alive at 3, 5 and 10 years
e) % cognitive involvement
a) 5,000
b) 1 in 300
c) 10-15%
d) 3 years - 50%
5 years - 25%
10 years - 5-10%
e) 35% cognitive involvement, and 15% develop FTD
EMG
- sensitivity for MND diagnosis
- findings in MND
60% - not a diagnostic test, used to support a diagnosis
- Active denervation (spontaneous activity of motor nerves/ muscle end plate - fibrillations, fibrillation potentials, and positive sharp waves seen)
- Chronic denervation/ reinnervation (disorganisation in motor unit action potentials due to death of motor neurons - long duration motor unit potentials (MUPs) seen, and reduced number of MUPs)
Mimics and chameleons in MND
a) Progressive, painless, paralysis
b) LMN syndromes
c) UMN syndromes
https://pn.bmj.com/content/13/3/153 (Turner et al)
https://www.ncbi.nlm.nih.gov/books/NBK560774/
a) Progressive, painless, paralysis:
i) Genetic disorders – Spinal muscular atrophy, Kennedy’s disease, hexosaminidase deficiency, mitochondrial disease, triple-A (Allgrove syndrome), polyglucosan body disease, hereditary spastic paraparesis, and adrenoleukodystrophy.
ii) Toxicity or metabolic disorders
– Radiation myelopathy
- thyrotoxicosis
- hyperparathyroidism
- B12 deficiency
- lead poisoning
- mercury poisoning
- copper deficiency
iii) Infectious diseases – Post-polio syndrome, Lyme disease, and HIV.
iv) Immunological or inflammatory syndromes
– Paraproteinemic neuropathy,
- conduction block neuropathy,
- Sjogren’s syndrome
- Inclusion body myositis
- Gluten sensitivity
- myasthenia gravis
- polymyositis / post-polio syndrome
v) Structural diseases – Spondylotic myelopathy, the base of skull lesions, foramen magnum lesions, intrinsic or extrinsic cord tumors, and lumbosacral radiculopathies.
vi) Miscellaneous condition – Cramp fasciculation syndromes, paraneoplastic disease, lymphoproliferative disease, and paraneoplastic neuromuscular disease
- stiff person syndrome (anti-GAD, truncal stiffness)
b) LMN syndromes:
- Brachial neuritis
- MMN
- Monomelic amyotrophy
- Kennedy’s disease
- Radiculopathy
- Mono/polyneuropathy
c) UMN syndromes:
- PLS
- HSP
- B12 deficiency, copper deficiency
- Primary progressive MS
- Adreno-leukodystrophy
Features to support trial of IVIG in a progressive motor neuropathy
- Significant abnormalities on nerve conduction studies, for example, conduction block or demyelination
- Monomelic slowly progressive lower motor neurone presentations, especially distal
- Anti-GM1 antibody positivity with no definite upper motor neurone signs
- Significantly raised cerebrospinal fluid protein
- Evidence of an underlying malignancy without resectable tumour
Findings that support MND diagnosis
a) Typical areas of weakness
b) Typical pattern of weakness
c) Typical examination findings
d) Features that suggest alternate/dual pathology
a) - Footdrop with positive Babinski in this foot
- Finger drop (though think MMN) or wrist drop
- Dysarthria
b) - 3 Ps - painless, progressive paralysis
- Generally weakness will progress in that limb first, then affect contiguous area (e.g. if starting in right leg, will then progress to involve left leg, or right arm)
- Should have wasting with the weakness
- Neck weakness common (vs cervical myeloradiculopathy)
- Bulbar weakness usually with speech slurring, followed by dysphagia
c) - UMN signs in same territory as the weakness
- Generalised fasciculations (often over the deltoids)
- Jaw jerk, tongue wasting and fasciculations (but often confused with ‘tongue tremor’)
- Frontal release signs - glabellar, snout, rooting, palmomental
- Split-hand sign (weakness/wasting greater in thenar and FDIO/APB vs ADM and hypothenar) and wasting of FDIO
d) - Significant sensory involvement (vs cervical myeloradiculopathy)
- Absence of wasting in weak muscles
- Fatigability/ relapsing or remitting course / very slow progressing
- Ocular involvement - think MG
- Finger flexion weakness with relative sparing of other muscles (think IBM)
- Slow progression (>2 years confined to one area)
- Lack of both upper and lower MN signs
PLS
- Pure UMN spastic weakness
- If lasting longer than 4 years, generally slowly progressive and only mildly life-limiting
Benign fasciculations
Benign fasciculations:
- common in younger patients, worse with exercise/caffeine/ alcohol
- Benign cramp/fasciculation syndrome has cramps also and improves with carbamazepine
- No associated weakness
MMN
a) prevalence vs MND
b) weakness pattern vs MND
c) other signs
d) investigation findings
a) 10x rarer than MND
b) - Slowly progressive asymmetrical distal LMN weakness (no UMN signs)
- Younger than MND (mean 40, none over 70) and more males
- Predominantly upper limb - Finger/wrist drop common.
- 1/3 have foot drop.
- Generally weakness without significant wasting. May be worse in the cold.
- No bulbar involvement, very very rare for respiratory sx
c) - Fasciculations localised to affected area (generalised in MND) and cramps common.
- Often hypo/areflexic affected limb
d) - NCS - conduction blocks
- Positive Anti-GM1 in 50%
d) - IVIG often effective*.
- Likely symptom recurrence without maintenance via IVIG.
- If fails, try rituximab/cyclophosphamide. No benefit from steroids/PLEX
*Practice points proposed by the European Federation of Neurological Societies and the Peripheral Nerve Society suggest:
- IVIG induction dose of 2 g/kg over 2 to 5 days
- maintenance IVIG of 1 g/kg every 2 to 4 weeks or 2 g/kg every 1 to 2 months as guided by treatment response.
Brachial neuritis
a) Other names
b) Clinical presentation
c) Investigations
a) Parsonage-Turner syndrome, or neuralgic amyotrophy
b) - Usually unilateral arm/neck/shoulder pain
- Then progresses to weakness, but slow recovery over months usually
- 10% bilateral
- Very rarely can cause bilateral diaphragmatic palsy and orthpnoea with need for NIV
- May have preceding infection or vaccination
c) NCS
Kennedy’s disease (spinobulbar muscular atrophy)
a) What is it?
b) Epidemiology
c) Pattern of weakness
d) Signs supportive on examination
e) Other features
f) Investigations
a) - X-linked recessive - mutation - trinucleotide repeat in 1st exon of androgen receptor gene (diagnostic)
b) - Affects men (X-linked)
- Onset usually in 30s-40s
c) - LMN pattern of slowly progressive symmetrical weakness of limbs and bulbar region
- May cause respiratory muscle weakness, but often not life-limiting
d) - Fasciculations common and where present over the chin, highly suggestive of Kennedys
- Tongue wasting common
e) - Sensory involvement common
- Gynaecomastia/ infertility
- Tremor common (although 10% MND have tremor)
f) Genetic testing
Motor-predominant CIDP
a) Pattern of weakness
b) Investigation findings
c) Treatment
a) - Often symmetrical, relapsing and remitting
b) - NCS shows demyelination
c) - Poor steroid response
- generally good with IVIG
Inclusion body myositis (IBM)
a) Pattern of weakness
b) Investigation findings
c) Management
a) - Usually patients >50 years old
- Slowly progressive finger flexion weakness*, thigh muscle weakness, can have footdrop
- May affect bulbar muscles, very rarely affects resp muscles
*finger flexors usually relatively spared in MND
b) - CK only mildly raised (2-10x normal range)
- Muscle biopsy - inclusion bodies (rimmed vacuoles) and inflammatory changes
- EMG may show neurogenic changes with fibrillation potentials
c) - Supportive treatment
- Steroids ineffective
HSP
a) Epidemiology
b) Pattern of weakness
c) Investigations
a) - onset middle age (younger than average MND)
- will usually have positive family history
b) - slowly progressive
- pure UMN weakness
- dorsal column sensory involvement
- sphincter disturbance common
- may have ataxia and dementia
c) SPAST gene positive in 40%
Adrenoleukodystrophy
a) What is it?
b) Subtypes and presentation of each
c) Investigations
d) Management
https://www.genomicseducation.hee.nhs.uk/documents/adrenoleukodystrophy/
a) - X-linked recessive disorder of ABCD1 gene causing disruption of VLCFA transport
- Causes VLCFA accumulation in one or more of the brain, myelin sheath and adrenal glands
b) A childhood cerebral form
- Onset age 4-10 years
- Progression variable but can be rapid, leading to death within 6-24 months of onset
- Children may show signs of dementia, behavioural problems, loss of fine motor skills, visual loss or other unexplained neurological symptoms and signs.
Adreno-myelo-neuropathy type
- men from their mid-20s onwards.
- Progressive paraparesis, sphincter problems, impotence and hypoadrenalism
- Symptoms may progress slowly over many decades, but rapid progression may occur in 10-20% of affected males.
Addison’s disease only form
- Disease onset can occur at any time
- May later on develop myelopathic features
Note: About 20% of carrier females develop neurologic manifestations of the condition; these symptoms are much milder than in males and do not usually develop until the fourth decade
c) - High levels of very long chain fatty acids (VLCFA) - Elevated concentrations of hexacosanoic acid (C26:0) with normal concentrations of phytanate and pristanate are the characteristic findings
- Gene testing for ABCD1 gene
- MRI brain and adrenal function testing
d) - Steroid replacement if hypoadrenalism
- Lorenzo oil is experimental - conflicting evidence that it slows but does not halt progression
- Diet high in medium chain fatty acids
Cervical myeloradiculopathy
a) vs MND
a) - Usually have sensory signs
- Very rare to have neck weakness vs MND
Monomelic amyotrophy
a) AKA
b) Presentation
c) What might NCS show
a) Hirayama’s disease, or,
Benign juvenile-onset monomelic amyotrophy
b) - Weakness of single upper limb (R:L affected 2:1)
- Progressive for 1-5 years, and then remains stable, may not show progression or recovery.
- More common in Asia, e.g. Japan
c) Diffuse denervation in affected limb
- Might show subclinical involvement in contralateral upper limb
Primary progressive MS
a) Presentation vs MND
b) Investigations
a) More slowly progressive spastic UMN weakness
b) = Positive CSF OCBs
- MRI demyelination in brain / spine
Gold Coast criteria for MND diagnosis
- Progressive motor impairment
AND
- UMN* and LMN** pathology in at least 1 body region (bulbar, cervical, thoracic, lumbosacral)
AND
- Exclusion of other differentials
*UMN features:
- Hyper-reflexia (especially in weak/wasted limb)
- Any pathological reflexes (Babinski, Hoffman, crossed adductor, snout, etc)
- Spasticity (velocity dependent tone increase)
- Poorly coordinated voluntary movement not attributable to LMN or Parkinsonian cause
**LMN features:
- Significant muscle wasting
- EMG abnormalities showing active denervation and chronic denervation/ reinnervation
