Long-term follow-up study on patients with Miyoshi phenotype of distal muscular dystrophy.

BACKGROUND AND PURPOSE: To describe the long-term follow-up of a cohort of 22 patients with the Miyoshi phenotype of distal muscular dystrophy (MMD). METHODS: A long-term clinical follow-up study was conducted. Patients were genotyped for dysferlin (MMD1) or anoctamin 5 (MMD3) mutations. Patients also underwent cardiological evaluation. RESULTS: There were 10 patients with MMD1, eight patients with MMD3 and four patients with linkage to chromosome 10 (MMD2). All patients deteriorated over 5.7 (range: 4.2-6.6) years of follow-up. Weakness increased significantly (P < 0.035) in all but the neck extensor, serratus anterior, and wrist flexor and extensor muscles. The decrease of strength was most pronounced in the iliopsoas (15%), toe extensors (15%), anterior tibial and peroneal muscles (10%). Patients with MMD1 showed early onset of the disease (mean 22 years) with typically symmetrical distribution of weakness starting in the calf muscles. Patients with MMD1 had a worse clinical course compared with patients with MMD3. Ninety percent of the former had to make use of a wheelchair within 15 years after onset of the disease, whereas patients with MMD3, who have a significantly later onset (mean 35 years) of asymmetrical calf muscle weakness and atrophy, remained ambulant during the first 15 years of their disease. None of the patients with MMD2 became fully confined to the wheelchair. None of the 22 MMD phenotype patients had heart disease. CONCLUSIONS: Patients with MMD1 have a worse clinical course compared with patients with MMD3. There are no cardiological abnormalities in all MMD categories.

Long-term outcome in polymyositis and dermatomyositis.

BACKGROUND: Although polymyositis and dermatomyositis are regarded as treatable disorders, prognosis is not well known, as in the literature long-term outcome and prognostic factors vary widely. AIM: To analyse the prognostic outcome factors in polymyositis and adult dermatomyositis. METHODS: We determined mortality, clinical outcome (muscle strength, disability, persistent use of drugs and quality of life) and disease course and analysed prognostic outcome factors. RESULTS: Disease-related death occurred in at least 10% of the patients, mainly because of associated cancer and pulmonary complications. Re-examination of 110 patients after a median follow-up of 5 years showed that 20% remained in remission and were off drugs, whereas 80% had a polycyclic or chronic continuous course. The cumulative risk of incident connective tissue disorder in patients with myositis was significantly increased. 65% of the patients had normal strength at follow-up, 34% had no or slight disability, and 16% had normal physical sickness impact profile scores. Muscle weakness was associated with higher age (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3 to 10.3). Disability was associated with male sex (OR 3.1; 95% CI 1.2 to 7.9). 41% of the patients with a favourable clinical outcome were still using drugs. Jo-1 antibodies predicted the persistent use of drugs (OR 4.4, 95% CI 1.3 to 15.0). CONCLUSIONS: Dermatomyositis and polymyositis are serious diseases with a disease-related mortality of at least 10%. In the long term, myositis has a major effect on perceived disability and quality of life, despite the regained muscle strength.

Polymyositis: an overdiagnosed entity.

BACKGROUND: According to widely used criteria (Bohan and Peter criteria, 1975), dermatomyositis (DM) is differentiated from polymyositis (PM) only by skin changes. More recent criteria also include histopathologic characteristics enabling the distinction between PM and DM and the differentiation of sporadic inclusion body myositis (s-IBM) from PM. The authors investigated the applicability of diagnostic features for diagnosing PM and DM. METHODS: The authors performed a retrospective follow-up study of 165 patients with 1) a previous diagnosis of myositis; 2) subacute onset of symmetric, proximal weakness; and 3) an evaluation between 1977 and 1998 excluding other neuromuscular disorders. RESULTS: The diagnoses at initial evaluation based on clinical, laboratory, and histopathologic criteria were PM, 9 (5%); DM, 59 (36%; 54 isolated, 3 with associated connective tissue disease [CTD], 2 with associated malignancy); unspecified myositis (perimysial/perivascular infiltrates, no PM or DM), 65 (39%; 38 isolated myositis, 26 with associated CTD, 1 with malignancy); and possible myositis (necrotizing myopathy, no inflammatory infiltrates), 32 (19%; 29 isolated myositis, 3 with associated CTD). At follow-up evaluation, five of the nine patients with PM had typical s-IBM features. None of the remaining four patients complied with the assumed typical signs of PM. Ten of the 38 patients with isolated unspecified myositis had been diagnosed with a CTD. CONCLUSIONS: Polymyositis is an overdiagnosed entity. At evaluation, more than half the patients with autoimmune myositis cannot be specifically diagnosed with polymyositis or dermatomyositis. A quarter of patients with isolated unspecified myositis subsequently developed connective tissue disease.

Necrotising myopathy, an unusual presentation of a steroid-responsive myopathy.

OBJECTIVE: To evaluate the clinical features, muscle pathology and response to treatment in patients with a necrotising myopathy, without mononuclear cell infiltrates. BACKGROUND: Mononuclear cell infiltrates in the muscle biopsy specimen are the diagnostic hallmark of the immune-mediated idiopathic inflammatory myopathies (IIM). In patients with the typical clinical features of IIM, absence of these infiltrates in the muscle biopsy specimen casts doubt on the diagnosis and leads to uncertainty about therapeutical strategies. METHODS: A detailed description is given of the clinical, laboratory, and histopathological features of eight patients suspected of having an idiopathic inflammatory myopathy, in whom mononuclear cell infiltrates in their muscle biopsy specimens were lacking. RESULTS: Eight patients (five men, three women, age range 40-69 years) had severe, symmetrical proximal weakness with a subacute onset. There were no skin abnormalities suggesting dermatomyositis. Serum creatine kinase activity was more than 10 times elevated. Repeated muscle biopsy specimens, taken from a symptomatic muscle prior to immunosuppressive treatment showed widespread necrosis, regeneration, and atrophy of muscle fibres, but no mononuclear cell infiltrates. Known causes of necrotising myopathy were excluded. Three patients had a malignancy. Adequately dosed and sustained immunosuppressive treatment eventually resulted in normal or near normal muscle strength in seven patients. One patient showed marked improvement. CONCLUSION: Occasionally, patients who clinically present as an idiopathic inflammatory myopathy may lack mononuclear cell infiltrates in their muscle biopsy specimens. This subacute-onset progressive necrotising myopathy should not deter the clinician from timely and appropriate treatment as we consider this myopathy to be steroid-responsive with a possible immune-mediated pathogenesis.

Efficacy of sumatriptan nasal spray in recurrent migrainous headache: an open prospective study.

OBJECTIVE: To evaluate the effectiveness of sumatriptan 20 mg via nasal spray and 100-mg tablets in treating migrainous headache in patients without a concomitant migraine diagnosis. METHODS: We prospectively investigated the efficacy of sumatriptan 20 mg via nasal spray and 100-mg tablets in patients with a history of at least 5 moderate to severe headache attacks lasting 2 to 72 hours that consistently did not meet the International Headache Society (IHS) criteria for migraine or episodic tension-type headache. RESULTS: Nineteen headache attacks classifiable as migrainous disorder without aura (IHS 1.7) were evaluated in 13 patients using 20-mg sumatriptan nasal spray within a 10-week period. A 2-point decrease in headache severity on a four-point scale was achieved in 74% (95% confidence interval [CI], 50% to 89%) of the attacks within 2 hours. The pain-free incidence (a reduction in headache severity from moderate or severe to none) was 37% (95% CI, 17% to 63%) after 2 hours. Ten patients completed the second part of the study, taking oral sumatriptan for 14 migrainous attacks: a 2-point decrease in headache severity was achieved in 38% (95% CI, 13% to 71%) of the attacks within 2 hours and in 77% (95% CI, 48% to 92%) within 4 hours. CONCLUSION: This is the first prospective study to show that intranasal or oral sumatriptan may be effective in patients experiencing moderate to severe headache attacks which consistently do not fulfill the IHS criteria for migraine or episodic tension-type headache.

[Vomiting as a first neurological sign of brain tumors in children]. / Braken als eerste neurologische symptoom van een hersentumor op de kinderleeftijd.

Four children (two boys aged 1.5 and 10 years and two girls aged 2 and 9 years) vomited for one-half to four weeks. In one child, ataxia was later also noted and another tilted his head constantly to the left, but this was initially not alarming. In all four cases CT revealed a brain tumour, for which they were operated. Postoperatively, one child had residual tumour tissue that caused no further problems, in two children the tumour was completely excised with no further symptoms and no recurrence in the following 2 years, and in one child complete excision was not possible so that chemotherapy and radiotherapy were given, but metastases nevertheless developed 10 months later and the child died. Vomiting is common in children and in most cases the result of infectious or gastrointestinal causes. Intracranial pathology also can cause vomiting, both by increased intracranial pressure and by direct stimulation of the vomiting centre in the brainstem. Brain tumours in children often lack specific neurological signs in their clinical presentation. Intractable or chronic vomiting without nausea or deregulation of the water and electrolyte balance could therefore indicate the presence of an intracranial process, even when other neurological signs are absent.

[Three patients with divergent presentations of idiopathic inflammatory myopathy]. / Drie patiënten met uiteenlopende presntaties van idiopathische inflammatoire myopathie.

The group of idiopathic inflammatory myopathies encompasses polymyositis, dermatomyositis and inclusion body myositis. These diseases share the following features: progressive muscle weakness, an increase in serum creatine kinase activity and the presence of mononuclear cell infiltrates in the muscle biopsy. Polymyositis, dermatomyositis and inclusion body myositis are differentiated on the basis of the distribution of muscle weakness, and specific histopathological features. Many specialties may see these patients as the clinical presentation can vary widely and may be atypical, requiring further diagnostic procedures. A 40-year-old man with a heliotrope rash and periorbital oedema, but no muscle involvement, was diagnosed with dermatomyositis sine myositis. He was successfully treated with corticosteroids but died later of cardiac failure. A 72-year-old man with a pulmonary malignancy subsequently developed the clinical features of dermatomyositis. Steroid therapy diminished the complaints but he died of pulmonary embolism. A 54-year-old woman with the clinical features of inclusion body myositis did not have rimmed vacuoles in her muscle biopsy specimen and was initially erroneously diagnosed with polymyositis, for which she was treated with corticosteroids, but without beneficial effect.

Is cardiovascular disease a risk factor in the development of axonal polyneuropathy?

OBJECTIVES: To determine if cardiovascular disease may be a risk factor in the development of chronic idiopathic axonal polyneuropathy (CIAP). METHODS: In this incidence case-control study, the prevalence of cardiovascular disease and risk factors in 97 patients with CIAP (mean age 67.5 (SD 7.9) years) and the prevalence of neuropathic features in 97 patients with peripheral arterial disease (PAD) (mean age 67.1 (SD 7.3) years) were investigated. The results were compared with those for 96 age and sex matched controls without diagnosed PAD or polyneuropathy (mean age 67.5 (SD 9.1) years). In a randomly chosen subgroup of 23 patients with CIAP, 42 patients with PAD, and 48 controls, an electrodiagnostic investigation was performed. RESULTS: Patients with CIAP more often had manifest cardiovascular disease and cardiovascular risk factors than controls (stroke 18% v 6% of patients, odds ratio (OR) 3.2 (95% confidence interval (CI) 1.8 to 5.9); heart disease 29% v 15%, OR 2.4 (95% CI 1.2 to 4.9); family history of cardiovascular disease 42% v 21%, OR 2.8 (95% CI (1.5 to 5.2); hypertension 56% v 39%, OR 2.0 (95% CI 1.1 to 3.6); hypercholesterolaemia 46% v 21%, OR 3.3 (95% CI 1.5 to 7.3); current smoking 38% v 23%, OR 2.1 (95% CI 1.1 to 3.9)). The prevalence of cardiovascular disease and cardiovascular risk factors was lower than in patients with PAD. Patients with PAD more often had polyneuropathy than controls (15% v 5%, OR 3.3 (95% CI 1.1 to 10.0)). There was a trend towards lower nerve conduction velocities and lower amplitudes on electrodiagnostic investigation compared with controls. CONCLUSION: This study shows that cardiovascular disease and CIAP often coexist, and therefore cardiovascular disease may be a cofactor in the development of CIAP.

Effects of medication use on health state in postictal migraineurs.

We investigated whether headache-free patients with migraine report a lower health state compared with healthy controls, and whether health state is differently affected during the postattack period after using sumatriptan versus habitual nonvasoactive medication. Mood, health state, and personality questionnaires were administered once during an interictal period and twice within 30 hours after different migraine attacks treated with sumatriptan or habitual nonvasoactive medication. Twenty migraineurs without aura, 10 migraineurs with aura, and 30 matched and headache-free controls participated in this study. During an interictal period, patients with migraine reported more problems regarding social activities and pain compared with healthy controls. During the postictal period, mood (fatigue and emotional state) was negatively affected by an attack that was treated with habitual medication, whereas health state (physical pain, social activities, current pain) was similar to the migraine-free period. Sumatriptan treatment had beneficial effects on aspects of health state and mood during the postictal period.

[Diagnostic image (29). Adult form of proximal spinal muscular atrophy]. / Diagnose in beeld (29). Adulte vorm van proximale spinale spieratrofie.

A 58-year-old man developed slowly progressive weakness of both legs due to the adult form of proximal spinal muscular atrophy.

Interictal and postictal contingent negative variation in migraine without aura.

Cortical hyperexcitability is thought to explain the more enhanced contingent negative variation (CNV) amplitudes and impaired CNV habituation that have been found during the interictal period in migraine without aura. These CNV characteristics have been shown to normalize to the level of healthy controls during an attack. This study aimed to replicate the interictal findings, and additionally examine whether migraineurs show reduced CNV amplitudes during the postattack period. Of 12 patients with migraine without aura and their sex- and age-matched healthy controls, CNV characteristics were recorded once in an interictal period, once during the postattack period within 30 hours after an attack that was treated with sumatriptan, and once after an attack that was treated with habitual nonvasoactive medication (counterbalanced). The present results did not confirm the enhanced CNV early and late wave amplitudes or impaired habituation, and cortical hyperexcitability that have previously been reported in the interictal period in patients with migraine without aura. During the postattack period, a decrease in CNV early and late amplitudes was found but only after sumatriptan use. This reduction in CNV amplitudes was most prominent over the frontal cortex and could reflect cortical hypoexcitability, possibly related to a suppression of central catecholaminergic activity by sumatriptan.

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study.

OBJECTIVES: To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism. METHODS: A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment. RESULTS: In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6 months). CONCLUSIONS: Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.

Benign prognosis in idiopathic hyper-CK-emia.

We report on the long-term follow-up in 31 patients with idiopathic hyper-CK-emia. At referral, all patients underwent a neurological interview and examination. Ancillary investigations included an open muscle biopsy and electromyography (EMG) in almost all, and other ancillary tests in some patients. After a follow-up period of 7.2 (mean; range 4-18) years, 74% of the patients had a final evaluation. The most common complaints at referral were fatigue and myalgia. EMG and muscle biopsy demonstrated minor, non-diagnostic abnormalities in 30 and 71% of patients, respectively. At follow-up, the pattern and the number of complaints had not changed substantially. One patient developed a sensory polyneuropathy. Neurological abnormalities were absent in all other patients. In conclusion, long-term follow-up of patients with idiopathic hyper-CK-emia does not reveal clinical deterioration. It seems justifiable to refrain from routine long-term follow-up in these patients.

Interictal and postictal cognitive changes in migraine.

The question whether symptom-free migraine patients show cognitive impairments compared to matched control subjects is addressed, and also whether migraine patients show transient cognitive impairments induced by an attack. The Neuropsychological Evaluation System (NES2) was administered once in an interictal period and twice within 30 h after different migraine attacks. Since cognitive impairments could be related to attack duration or severity, cognitive performance was compared during a postictal period after sumatriptan use and during a postictal period after habitual nonvasoactive medication use. Twenty migraineurs without aura, 10 migraineurs with aura, and 30 matched headache-free controls participated in the study. During a headache-free period, migraineurs without aura responded as quickly as controls, while migraineurs with aura were slower than controls during all tasks specifically requiring selective attention. These effects were not aggravated by a preceding migraine attack, irrespective of medication use and attack duration.