Raven Neurology Review -4- Neuromuscular

• Episodic weakness without myotonia
• Lasts for hours to days!
• Often bought on by exercise, awakening from sleep, cold temperatures or eating high carb/sodium meals.
• Autosomal dominant - SCN4A or CACNA1S
• Carbonic anhydrase inhibitors or potassium sparing diuretics

• Episodic weakness without myotonia
• Lasts for minutes to hours
• Bought on by fasting or exercise
• AD - SCN4A
• Thiazide diuretics

• Thyrotoxic periodic paralysis
• Treat with propranolol
• KCNJ18 mutation

• HNPP
• CMT1A

• This is a demyelinating neuropathy.
• Causes onion-bulbing of Schwann cells due to repeated episodes of remyelination.
• Causes decrease conduction velocity with no conduction block.

• Type 1 - AD - Demyelinating
• Type 2 - AR - Axonal
• Type 3 - AR - Demyelinating

• Fluoroquinolones
• All the anti-arrhythmics
• Aminoglycosides
• Magnesium

• Single fibre EMG
• Shows jitter and blocking

• Weakness, resp failure, arthrogryposis
• Will resolve in a month

Typer 2 fibre atrophy

Early motor unit recruitment

• Over the age of 50.
• M>F.
• Proximal wasting in the lower limbs and distal in the upper.
• Often has bulbar involvement
• Elevated CK

• F>M
• Associated rash on face/trunk/knuckles (gottron's)
• Increased risk of malignancy

• Anti-Jo1
• Perifasicular atrophy

Rimmed vacuoles best seen with trichrome stain.

• Campylobacter jejuni infections
• MMN

Motor axonal neuropathy

• Causes a demyelinating polyneuropathy similar to GBS
• AND a pseudomembranous pharyngitis

Block the release of glycine and GABA

• Kennedy's disease
• Typically bulbar symptoms early, then widespread wasting and weakness.
• Prominent perioral fasiculations
• Gynaecomastia

• Androgen receptor gene
• X linked recessive
• Trinucleotide repeat disorder - CAG

• Parsonage-Turner
• Idiopathic brachial neuritis
• Gets better with time
• Commonly provoked by excessive exercise, childbirth, infection, vaccination, surgery and IVDU.
• The hereditary form is Autosomal dominant
• Can also affect the lumbosacral plexus?

• Tomaculi! Sausage like areas of thickening!
• PMP 22 deletion

Both autosomal dominant

• Atrophy in the spinal cord and motor strip.
• Loss of pyramidal betz cells in the cortex and alpha motor neurons in the anterior horn.
• Bunina bodies are found in the cell bodies of the LMN.
• Muscle pathology shows muscle fibre type grouping.
• EMG shows widespread denervation

Inhibits glutamate release.

• DMPK gene - CTG trinucleotide repeat with anticipation
• Autosomal dominant

• Dried spot test
• Glycogen filled lysosomes - they stain with PAS (periodic acid-schiff)

• Onset in 2nd-4th decade
• Weakness of trunk, proximal muscles and diaphragm.
• Electrical myotonia without clinical myotonia

Anatomical variant in which the median nerve innervates muscles in the ulnar nerve distribution.

Elbow and wrist flexion and lateral forearm sensation

• Elbow, wrist and finger extension and shoulder abduction
• Sensation to posterior hand and arm.

• Thumb and finger flexors, intrinsic hand muscles
• Medial forearm sensation.

Steroids

Slowly progressive, asymmetric, multifocal weakness without very much wasting.

• A type of Spinal muscular atrophy.
• X-linked disorder that presents with Bulbar weakness, prominent perioral fasiculations and androgen sensitivity (gynaecomastia, testicular atrophy, azoospermia)
• CAG repeat - polyglutamine

• A type of SMA
• Onset in adolescence 
• Progressive bulbar palsy with Bilateral sensorineural hearing loss
• tongue atrophy, fasiculations and dysphagia

• Juvenile monomelic amyotrophy
• Predominantly affects C7-T1 nerve roots

Weakness, wasting and fasiculations.

SMN gene involved in mRNA splicing

• SMA 1 and 2 present in childhood
• SMA 3 - adulthood - usually with a CK 10x normal - also known as wohlfart-kugelberg-welander

• Descending, asymmetrical weakness involving face, scapula, upper arm, lower leg and hip girdle.
• Differs from the others due to prominent PAIN

• Retinal vasculopathy
• Sensorineural hearing loss

• More common in French Canadians and Bukhara Jews
• Autosomal dominant condition 
• Presents in 5th/6th decade of life with progressive ptosis and dysphagia
• Classic muscle biopsy finding of Intranuclear tubular filaments

• Conus is symmetrical with mixed signs and early sphincter involvement
• Cauda is asymmetric with LMN signs only and late sphincter involvement

Its the common peroneal!!

• Severe painful paraesthesia over the lateral thigh
• Caused by compression of the lateral femoral cutaneous nerve (innervated by L2/3)
• Caused by obesity, pregnancy, tight belts, tumors, prolonged sitting, diabetes and excessive wt loss.

• Associated with Steroid and NM blocking drug usage
• Selective loss of myosin from myofibrils
• "Myosin losing myopathy"

• Myotonic discharges with waxing and waning amplitude
• The dive bomber pattern

• Paramyotonia congenita.
• Its 'para' because it gets worse with exercise rather than better
• Caused by a mutation in SCN4A gene

Pompe's - acid maltase deficiency

• Myophosphorylase deficiency.
• Exercise intolerance from childhood including myalgia, cramps, normal exam, normal lactate
• Raised CK and Myoglobinuria

median sensory nerve conduction

• Kearns-Sayre-Syndrome
• Progressive external opthalmoplegia
• Pigmentary retinopathy
• Cerebellar ataxia
• High CSF protein
• Leukoencephalopathy and basal ganglia calcification

• CMT1 = Autosomal dominant and demyelinating
• CMT2 = Autosomal dominant and axonal
• CMT3 = AD Childhood onset with delayed motor milestones and severe demyelination
• CMT4 = Autosomal recessive

• A definite diagnosis of MND based on revised El Escorial criteria 
• Bulbar onset,
• Presentation after 80 years of age and
• Lower FVC at diagnosis

Family history of MND does not affect prognosis.

• Longer delay from onset to diagnosis,
• Onset before the age of 40 years and
• Spinal onset of disease carry a better prognosis.

• Progressive upper motor neurone disorder,
• Often beginning in the 5-6th decade of life, 
• Accounts for 1-4% of MND.
• More benign prognosis than ALS.
• Symptoms usually start in the legs. Patients report stiffness, poor balance and falls.
• Bulbar symptoms can such as dysarthria and dysphagia eventually develop.
• Urinary dysfunction is sometimes reported.

• Fasciculations and muscle atrophy are absent.
• More benign prognosis
• ALL UMN with stiff gait

The sniff nasal pressure test

Only 10% make full recovery at 3 years

• Autoimmune Autonomic failure.
• Half of cases are assoc with gnACHr (ganglionic nicotinic)
• Paraneoplastic forms are also seen in assoc with SCLC and Anti-Hu

• Decreased inner thigh sensation
• Weakness of hip adduction and rotation.

GM1

GT1a

Progressive encephalomyelitis with Rigidity and Myoclonus

<1%, Absence of ACHr antibodies has an NPV of <1%

The presence of lymphoplasmacytoid cells with anaemia, IgM kappa monoclonal gammopathy, and peripheral neuropathy suggests a diagnosis of Waldenström’s macroglobulinaemia (WM). CNS involvement by malignant cells is a rare complication of WM referred to as Bing-Neel syndrome (BNS) which usually manifests a few years after the diagnosis of WM.

Repeat the CT chest - thymomas recur

Cerebellar ataxia

Platinum-based ones

• Vitamin B6 - pyridoxine
• often used in body building diets

• Most common mutation found in adult onset
• Autosomal dominant Hereditary spastic paraplegia – accounts for 40%
• 20% of patients have cognitive impairment

CMV infection

• Greater severity of multiorgan dysfunction,
• Female sex
• Hyperglycemia
• Prolonged mechanical ventilation (not prolonged time of illness before ventilation)

• Intestinal pseudo-obstruction.
• Also causes peripheral neuropathy, ptosis and opthalmoparesis.
• Caused by a mutation in the Thymidine phophorylase gene which is an autosomal gene but causes problems mostly in mtDNA.
• Can be thought of as a mitochondrial disorder in its presentation but is autosomal at a molecular level.

• 95% of FSHD patients have Abberant expression of DUX4 – the fewer D4Z4 repeats you have, the more expression occurs.
• 5% have no problem with D4Z4 but instead have a mutation in SMCHD1 which allows the DUX4 gene to be read more easily

When FVC is significantly reduced

SMA type 1

• Onasemnogene abeparvovec
• one-off IV dose of AAV-9 delivered SMN1 gene replacement therapy.