Neuromuscular Diseases A Practical Guideline - part 8

330 Biopsy is not usually performed, as the EMG and genetic information is decisive. Differential diagnosis Therapy Prognosis References HNPP may resemble CMT, but the occurrence of pressure palsies and the EMG findings make HNPP distinctive. Inflammatory neuropathies like CIDP and multifocal motor neuropathy (MMN) with conduction block should also be considered. MMN does not usually show signs of sensory impairment with electrodiagnostic studies. The electrodiagnostic findings in CIDP are symmetri-cal. HNPP is usually treated with support. Surgical intervention for entrapment is controversial, as manipulations frequently cause nerve injury. Genetic counseling can be provided to family members. The course of HNPP is usually benign. Andersson PB, Yuen E, Parko K, et al (2000) Electrodiagnostic features of hereditary neuropathy with liability to pressure palsies. Neurology 54: 40–44 Chance PF (1999) Overview of hereditary neuropathy with liability to pressure palsies. Ann NY Acad Sci 883: 14–21 De Jonghe P, Timmerman V, Nelis E, et al (1997) Charcot-Marie-Tooth disease and related peripheral neuropathies. J Peripher Nerv Syst 2: 370–387 Pareyson D, Taroni F (1996) Deletion of the PMP22 gene and hereditary neuropathy with liability to pressure palsies. Curr Opin Neurol 9: 348–354 This is trial version www.adultpdf.com 331 Porphyria Genetic testing NCV/EMG Laboratory Imaging Biopsy ++ ++ Porphyria causes axonal degeneration with some regions of demyelination. Patients typically present with debilitating abdominal pain, changes in urine color, constipation, and vomiting. Neuropathy usually follows the abdominal signs by several days, and resembles AIDP, with pain and potentially asymmet-ric weakness. CNS disturbances can precede neuropathy, including agitation, psychosis, seizures, and eventually coma. Weakness can involve the face and respiratory muscles. Autonomic dysfunction is common. In some forms of porphyria, skin blisters can accompany an acute attack. Attacks can be precipitated by drugs that stress liver function, fasting, stress, and alcohol. Porphyria is rare and caused by disruption of heme biosynthesis. Subtypes of porphyria result from dysfunction of each of the enzymes in the heme synthetic pathway, but only the subtypes that involve liver enzymes cause neuropathy. These subtypes are aminolevulinic acid dehydrase deficiency, acute intermit-tent prophyria, hereditary coproporphyria, and variegate porphyria. Electrodiagnosis shows predominantly motor impairment. The primary diagnositic tool for an acute attack is a rapid urine test for porphobilinogen. Genetic testing is useful for exact diagnosis and for family counseling. AIDP does not involve such intense abdominal pain. Changes in urine color should raise suspicion of porphyria. Poisoning by lead, arsenic, or thallium can appear similar to porphyria, and even cause increases in urine porphobilino-gen. The most important treatment for an acute attack is IV heme, with attention to carbohydrate and fluid maintenance. Hyponatremia may occur and needs to be corrected. Any precipitating drugs should be withdrawn. Pain and vomiting should be treated. CNS disturbances can be difficult to treat, although gabapen- tin may help control seizures. Anatomy/distribution Symptoms Clinical syndrome/ signs Pathogenesis Diagnosis Differential diagnosis Therapy This is trial version www.adultpdf.com 332 In the long term, prevention is the best therapy. Drugs that can precipitate attacks should be avoided. Some porphyria can be triggered by hormonal changes during menstruation, and these cases can be very difficult to control. Prognosis References Heme therapy is very effective at quelling acute attacks, although mortality may still be as high as 10%. Most patients recover on the whole, but severe neuropathy may be resistant because of the axonal degeneration. Kochar DK, Poonia A, Kumawat BL, et al (2000) Study of motor and sensory nerve conduction velocities, late responses (F-wave and H-reflex) and somatosensory evoked potential in latent phase of intermittent acute porphyria. Electromyogr Clin Neurophysiol 40 (2): 73–79 Meyer UA, Schuurmans MM, Lindberg RL (1998) Acute porphyrias: pathogenesis of neurological manifestations. Semin Liver Dis 18 (1): 43–52 Muley SA, Midani HA, Rank JM, et al (1998) Neuropathy in erythropoietic protoporphyr-ias. Neurology 51 (1): 262–265 Wikberg A, Andersson C, Lithner F (2000) Signs of neuropathy in the lower legs and feet of patients with acute intermittent porphyria. J Intern Med 248 (1): 27–32 This is trial version www.adultpdf.com 333 Other rare hereditary neuropathies Many other hereditary neuropathies have been identified, often in just a handful of families in a particular ethnic and geographic region. Several of the more common disorders are summarized in the chart below. X-linked CMT is more common than CMT-2, and Riley-Day syndrome is fairly common in Ashkenazi Jews. All are treated symptomatically and are gradually progressive. Neuropathy CMT-3 (Dejerine-Sottas disease) see Fig. 16 CMT-4 X-linked CMT Hereditary Sensory Neuropathy (HSN) Riley-Day syndrome (familial dysautonomia) Genetics Autosomal dominant, sporadic, or recessive. Linked to mutations or deletions in PMP22 or Po. Autosomal recessive. Several subclassifications have been identified in different families with distinct loci. X-linked dominant, more severe in males. Mutation in Connexin 32. Autosomal dominant neuropathy identified in several Australian families. Autosomal recessive, occurs in 1:50,000 Ashkenazi Jews. Clinical features Severe demyelinating neuropathy of childhood. Both motor and sensory involvement. Very slow NCVs. Demyelinating motor and sensory neuropathy with slow NCVs. Demyelinating neuropathy with axonal degeneration. Slow or intermediate NCVs. Genetic testing is available. Axonal sensory neuropathy. Normal NCVs. Severe small fiber neuro-pathy with pulmonary and renal complications. NCV is normal. Kuhlenbaumer G, Young P, Hunermund G, et al (2002) Clinical features and molecular Reference genetics of hereditary peripheral neuropathies. J Neurol 249(12): 1629–1650 This is trial version www.adultpdf.com 335 Neuromuscular transmission disorders and other conditions ... - tailieumienphi.vn