Color Atlas of Neurology (Thieme 2004)

Peripheral Neuropathies

Nonmetabolic Hereditary Neuropathies

(Tables 62 and 63, p. 396 f)

For neuropathies associated with systemic disease, see p. 280.

! Hereditary Motor–Sensory Neuropathy

The type I phenotype is produced by three different genotypes: CMT1 (autosomal domi-

(X-linked).

HMSN type II. CMT2A and B resemble HMSN type I but begin later, with only rare areflexia and no palpable thickening of peripheral nerves. CMT2C is characterized by vocal cord paralysis (hoarseness, inspiratory stridor), proximal and distal weakness, distal muscle atrophy, and areflexia.

HMSN type III. This rare polyneuropathy (eponym: Dejerine–Sottas disease) becomes manifest at birth or in childhood with generalized weakness, areflexia, and palpable nerve thickening. Hearing loss, skeletal deformity, and sensory deficits ( ataxia) ensue as the disease progresses.

!Hereditary Neuropathy with Pressure Palsies (HNPP)

HNPP is characterized by recurrent, transient episodes of weakness and sensory loss after relatively mild compression of a peripheral nerve (ulnar, peroneal, radial, or median nerve). There may be evidence of a generalized polyneuropathy or a painless plexopathy. The “sausagelike” pathological changes seen on sural nerve biopsy are the origin of the alterna-

332 tive name, tomaculous neuropathy (from Latin tomaculum, “sausage”).

Metabolic Hereditary Neuropathies

Other members of this class are listed in the section on metabolic diseases (p. 306 ff).

! Porphyria

Among the known porphyrias, four hepatic types are associated with encephalopathy and peripheral neuropathy: variegate porphyria, acute intermittent porphyria, hereditary coproporphyria, and δ-aminolevulinic acid dehydrase deficiency (autosomal recessive; the others are autosomal dominant). The porphyrias are hereditary enzymopathies affecting the biosynthesis of heme. Severe peripheral neuropathy is seen during attacks of acute porphyria, which are most often precipitated by medications and hormonal influences (also fasting, alcohol, and infection). The manifestations of porphyria include colicky abdominal pain, pain in the limbs, paresthesiae, tachycardia, and variable degrees of weakness. Encephalopathy is manifest as confusion, lack of concentration, somnolence, psychosis, hallucinations and/or epileptic seizures. The diagnosis of porphyria is based on the demonstration of porphyrin metabolites in the urine and feces.

!Neuropathy Due to Hereditary Disorders of Lipid Metabolism

Polyneuropathy occurs in metachromatic leukodystrophy (p. 306), Krabbe disease (p. 307), abetalipoproteinemia (p. 300), adrenomyeloneuropathy (p. 384), Tangier disease (tonsillar hypertrophy, hepatosplenomegaly, low serum cholesterol, serum HDL deficiency), Fabry disease (punctate red angiokeratoma on buttocks and in the genital and periumbilical areas, retinovascular changes, corneal deposits, nephropathy, painful neuropathy; glycosphingolipid deposition due to α-galactosidase deficiency), and Refsum disease. The last is an autosomal recessive disorder of phytanic acid metabolism in which phytanic acid accumulation leads to tapetoretinal degeneration, night blindness, and a distal, symmetric polyneuropathy with peripheral nerve thickening. The CSF protein concentration is markedly elevated, but the CSF cell count is normal. The serum phytanic acid concentration is elevated.

Radial nerve pressure palsy

HNPP

Amyloid deposits (sural nerve, Congo red staining)

Foot ulcer/mutilation

Hereditary sensory neuropathy type I

Green birefringence (polarized light)

Amyloid neuropathy

Peripheral Nerve and Muscle

333

Peripheral Nerve and Muscle

334

Peripheral Nerve and Muscle

335

Myopathies

Muscular Dystrophies

The muscular dystrophies—myopathies characterized by progressive degeneration of muscle— are mostly hereditary.

336phinopathies and other forms of muscular dystrophy. DNA tests are used for the identification

of asymptomatic female carriers (in whom

muscle biopsy is hardly ever necessary), and for prenatal diagnosis.

! Treatment

The goal of treatment is to prevent contracture and skeletal deformity and to keep the patient able to sit and walk for as long as possible. The patient’s diet should be monitored to prevent obesity. The most important general measures are genetic counseling, social services, psychiatric counseling, and educating the patient on the special risks associated with general anesthesia. The type of schooling and employment must be appropriately suited to the patient’s individual abilities and prognosis. Physical therapy includes measures to prevent contractures, as well as breathing exercises (deep breathing, positional drainage, measures to counteract increased inspiratory resistance). Patients with alveolar hypoventilation may need intermittent ventilation with continuous positive airway pressure (CPAP) at night. Orthoses may be helpful, depending on the extent of weakness (night splints to prevent talipes equinus, seat cushions, peroneal springs, orthopedic corsets, leg orthoses). Home aids may be needed as weakness progresses (padding, eating aids, toilet/bathing aids, stair-lift, mechanized wheelchair, specially adapted automobile). Surgery may be needed to correct scoliosis, prevent contracture about the hip joint (iliotibial tract release), and correct winging of the scapula (scapulopexy/scapulodesis) and other deformities and contractures. Intracardiac conduction abnormalities (e. g., in Emery–Dreifuss muscular dystrophy) require timely pacemaker implantation. Heart transplantation may be needed when severe cardiomyopathy arises in conjunction with certain types of muscular dystrophy (Becker, Emery– Dreifuss; Table 68, p. 400).

Myopathies

Weakness of mouth closure

Peripheral Nerve and Muscle

337

Myopathies

The Myotonias (Table 69, p. 401)

! Symptoms and Signs

In hypokalemic and hyperkalemic myotonia, there are irregularly occurring episodes of flaccid paresis of variable duration and severity, with no symptoms in between. The anal and urethral sphincters are not affected. In paramyotonia congenita, muscle stiffness increases on exertion (paradoxical myotonia) and is followed by weakness. Cold exposure worsens the stiffness.

! Diagnosis

The diagnosis can usually be made from the personal and family history, abnormal serum potassium concentration, and molecular genetic findings (mutation of the gene for a membrane ion channel). If the diagnosis remains in question, provocative tests can be performed between attacks. The induction of paralytic attacks by administration of glucose and insulin indicates hypokalemic paralysis, while their induction by potassium administration and exercise (e. g. on a bicycle ergometer) indicates hyperkalemic paralysis. The diagnosis of paramyotonia congenita is based on the characteristic clinical features (paradoxical myotonia, exacerbation by cold exposure), autosomal dominant inheritance, and demonstration of the causative point mutation of the sodium channel gene.

! Treatment

Acute attacks. Milder episodes of weakness in hypokalemic disorders need no treatment, while more severe episodes can be treated with oral potassium administration. Milder episodes of weakness in hyperkalemic disorders also need no treatment; more severe episodes may require calcium gluconate i. v., or salbutamol by inhaler.

Prophylaxis. Hypokalemic paralysis: Low-salt, low-carbohydrate diet, avoidance of strenuous exercise; oral acetazolamide or spironolactone.

Hyperkalemic paralysis: high-carbohydrate diet; avoidance of strenuous exercise and cold; oral hydrochlorothiazide or acetazolamide.

Myopathies

hand opening after grasping)

Ion channels for maintenance of transmembrane potential

Percussion myotonia (adduction of thumb on thenar percussion)

Myopathic facies, weakness of lid closure, atrophy of anterior neck muscles, myotonic cataract

Lingual percussion myotonia

Peripheral Nerve and Muscle

339

Peripheral Nerve and Muscle

Peripheral Nerve and Muscle

341