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Importance We describe a case of cramplike pain after a left thalamic ischemic stroke, a neglected type of central post-stroke pain and we describe its neuroanatomical correlates. Observations A 68-year-old right-handed man presented with right arm, leg, and flank cramplike pain noted upon awakening. Neurological examination was normal, with no evidence of objective sensory abnormalities. Because of the nature of the pain and the preserved sensory function, we first did not consider stroke as a potential cause, and suspected that pain was related to the combined effect of intense physical exercising on the right side and the use of statins. Diffusion-weighted magnetic resonance imaging showed an acute ischemic infarction within the left thalamus. By registering high-resolution 3 T T1-weighted and T2-weighted magnetic resonance images to the Talairach atlas, we showed the infarction is within the border between the pulvinar and the ventral posterior medial nuclei. Brodmann's areas 3, 1, 2, 4 and 6 were identified as the cortical correlates of the ischemic lesion by diffusion tensor tractography. Conclusions and relevance Thalamic cramplike pain should be recognized as a type of central post-stroke pain, probably produced by lesions localized to the border between the ventral posterior and pulvinar nuclei and connected to the ipsilateral primary somatosensory cortex and primary and secondary motor cortices.

Although progressive multifocal leukoencephalopathy (PML) cases showing responses to mefloquine therapy have been reported, the efficacy of mefloquine for PML remains unclear. We report on the failure of mefloquine therapy in two Japanese patients with PML unrelated to human immunodeficiency virus. One of the patients was a 47-year-old male who had been treated with chemotherapy for Waldenstrom macroglobulinemia, and the other was an 81-year-old male with idiopathic CD4 + lymphocytopenia. Diagnosis of PML was established based on MRI findings and increased JC virus DNA in the cerebrospinal fluid in both patients. Mefloquine was initiated about 5months and 2months after the onset of PML, respectively. During mefloquine therapy, clinical and radiological progression was observed, and JC virus DNA in the cerebrospinal fluid was increased in both patients. Both patients died about 4months and 2months after initiation of mefloquine, respectively. Further studies are necessary to clarify the differences between mefloquine responders and non-responders in PML.

Objective: To examine the utility of repetitive nerve stimulation (RNS) in the evaluation of peripheral nerve hyperexcitability (PNH). Background: PNH describes a group of disorders characterized by muscle cramps, twitching and stiffness. When severe, PNH may be characterized by the presence of continuous muscle fiber activity on routine needle electromyography (EMG). In milder forms of the disease, nerve hyperexcitability may be evidenced by the presence of after-discharges or cramp potentials following RNS. Methods: Fifty-four patients were prospectively recruited and classified into one of three groups—PNH, other neuromuscular disease and controls. We recorded and quantified the after-discharges and cramp potentials following RNS at 1, 5, 10 and 30 Hz. Results: The proportion of nerves with after-discharges and/or cramp potentials was significantly greater in the PNH group than the control group at both 5 Hz (p=0.03) and 10 Hz (p=0.01), as well as in the neuromuscular disease group compared to controls at 5 Hz (p=0.02). There was also a significant concordance between complaints of muscle cramps and fasciculations and the finding of after-discharges and/or cramp potentials at both 5 Hz (p=0.005) and 10 Hz (p=0.004). At a stimulation frequency of 10 Hz, the sensitivity of RNS for the diagnosis of PNH (primary or secondary) was 79% and the specificity was 88%. Conclusion: Our findings suggest that RNS at or below a stimulation frequency of 10 Hz (when positive) is a useful test for the diagnosis of PNH, whether it is primary or secondary.

Kennedy's disease, also known as bulbospinal muscular atrophy (BSMA), is a rare, adult-onset, X-linked, recessive trinucleotide, polyglutamine (poly-G) disorder, caused by expansion of an unstable CAG-tandem-repeat in exon 1 of the androgen-receptor (AR) gene on chromosome Xq11-12. Poly-Q-expanded AR accumulates in nuclei, undergoes fragmentation and initiates degeneration and loss of motor neurons and dorsal root ganglia. Phenotypically, patients present with weakness and wasting of the facial, bulbar and extremity muscles, sensory disturbances, and endocrinological disturbances, such as gynecomastia and reduced fertility. In the limb muscles weakness and wasting may be symmetric or asymmetric, proximal or distal, or may predominate at the lower or upper limb muscles. There may be mild to severe hyper-CK-emia, elevated testosterone or other sexual hormones, abnormal motor and sensory nerve conduction studies, and neuropathic or rarely myopathic alterations on muscle biopsy. BSMA is diagnosed if the number of CAG-repeats exceeds 40. No causal therapy is available but symptomatic therapy may be beneficial for weakness, tremor, endocrinological abnormalities, muscle cramps, respiratory failure, or dysphagia. The course is slowly progressive and the ability to walk lost only late in life. Only few patients require ventilatory support and life expectancy is only slightly compromised.

We report a case of motor neuron disease in which fasciculations and cramps progressed generally before the development of muscle wasting. After involvement of the upper and lower motor neurons became clinically manifest, widespread fasciculations and cramps persisted and accompanied pseudotetany. The present case suggests that spinal cord pathology of motor neuron disease can cause the abnormal excitability of the motor neurons, resulting in the development of generalized fasciculations and cramps.

We identified a novel stop codon mutation in the myophosphorylase gene in a Greek patient with typical symptoms of McArdle's disease. This is the first genetic study of myophosphorylase deficiency in a Greek family, showing that the proband was a compound heterozygous for the common “caucasian” mutation (R49X) and a new nonsense mutation (Y52X), both within exon 1. The new point mutation, a C-to-G transversion at codon 52, converts an encoded tyrosine to a stop codon. Our study confirms that the R49X is also present in the Greek population. The Y52X may represent a private mutation or a common mutation among Greeks. Our data further expand the already remarkable genetic heterogeneity of McArdle's disease. The prevalence of the Y52X mutation in Greek patients with McArdle's disease remains to be determined.

We report the clinical, neurophysiological, and immunocramps, either at rest or on exercise, in limb and trunk logical findings in a novel case, presenting with neuromuscles. Blood chemistry, including serum electrolytes, myotonia (NMT) and essential thrombocythemia (ET). calcium, phosphorus, creatine kinase, and thyroid function A 68-year-old was in good health until March 1988, tests, was normal. Anti-voltage-gated potassium channels when he begun experiencing progressing muscle cramps. (VGKC) antibodies were negative. Electrophysiologic These at first affected only his lower limbs and were testing revealed normal motor and sensory nerve conducbrought on by exercise. Later, they spread to affect his tion studies of the median, ulnar, sural, tibial, and common hands, arms, abdomen and thorax muscles. The cramps peroneal nerves, but needle recordings from resting musoften occurred while he was resting, and were always cles showed continuous activity of the motor units, preincreased by exercise, and were a cause of major disability. senting as single potentials or bursts of high frequency The patient had no other neurological symptoms. motor unit potentials in different limb muscles (abductor On admission, at another institution, physical examinapollicis brevis, flexor digitorum profundus, quadriceps tion was normal except that muscle twitching could be femori, biceps femoralis, gastrocnemius, and tibialis anseen, either at rest or on exercise, in limb and trunk terior). Ischemic block of the median nerve, lasting 4 min, muscles. Tone and power were normal and tendon reflexes did not modify the continuous muscle activity recorded were present. Plantar responses were flexor. There were no from the right abductor pollicis brevis. To define the origin sensory signs. Percussion did not elicit myotonia. Routine of this spontaneous activity, anesthetic block of the left laboratory analysis was negative and an electrophysiologic tibial and common peroneal nerves by local infiltration of study was considered normal. The patient was discharged 10 ml of 0.5% bupivacaine and 40 ml of 1% bupivacaine and treated with hydroxiquinine 200 mg daily. However, at the fibular head induced a complete nerve conduction the cramps persisted. block. Nevertheless, the involuntary muscle discharges In February 1991, routine laboratory analysis revealed a were still present, demonstrating the peripheral origin of persistently elevated platelet count of between 669 and the hyperexcitability. 9 772310 / l, and a diagnosis of essential ET was made on Therapy with phenytoin, 200 mg daily, only controlled the basis of the Polycythemia Vera Study Group criteria the cramps partially. However, his symptoms almost [1]. Therapy with hydroxyurea controlled the platelet completely disappeared following therapy with carbamazcounts, but the cramps remained unmodified. epine at a total dose of 600 mg a day. He is currently In May 1993, he was admitted to the Mostoles General asymptomatic. Hospital for further evaluation. On admission, the findings NMT is an acquired disorder of peripheral nerve hyperwere similar to previous observations with myokymia and excitability, characterized clinically by myokymia, cramps, especially induced by muscle activity, impaired muscle relaxation, and sometimes muscle weakness; there is often *Corresponding author. Tel.: 134-91-390-8666; fax: 134-91-390increased sweating and a raised creatine kinase level. The 8666. E-mail address: jbenitol@meditex.es (J. Benito-Leon) electrophysiological hallmark is the spontaneous firing of

In order to compare the efficacy of a daily dose of 300 mg hydroquinine hydrobromide and placebo in preventing frequent ordinary muscle cramp, we designed a randomized, double-blind, placebo-controlled study of three consecutive 2-week periods viz. a qualification period, a medication period and a wash-out period. Twenty healthy adult volunteers experiencing at least 3 muscle cramps a week (6 men, 14 women aged 38-78 yrs) were enrolled into this study, and 19 of them completed it. Hydroquinine hydrobromide (300 mg/day) was administered to group 1 (10 women) and placebo to group 2 (4 women, 6 men). The frequency, severity, duration and location of muscle cramps as well as short-term adverse drug effects were recorded in daily diaries. Compared with placebo the decrease in the mean number of muscle cramps (16.1 or 58%) in the active drug treatment group during the medication period was highly significant (Wilcoxon test p = 0.004). During the wash-out period this decrease partly persisted (8.9 or 33%). In this study a daily dose of 300 mg hydroquinine hydrobromide was effective in preventing frequent ordinary muscle cramp in healthy female volunteers. The effects of hydroquinine outlasted its administration. The drug was well tolerated.

A Spanish family transmits, as an autosomal dominant trait, a form of amyotrophic lateral sclerosis characterized by an unusually prolonged evolution of the disease in all affected members. Precocity and persistence of muscle cramps, presence of unilateral proximal segmental myoclonus and early abolition of ankle jerks are other clinical features conspicuous in this family. This type of hereditary ALS of non-chamorro origin and prolonged evolution is rare.

A model of the human neuromuscular disorders myophosphorylase deficiency and phosphofructokinase deficiency has been developed using intra-aortic injection of sodium iodoacetate in adult male rats. Iodoacetate selectively inhibits in vivo the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. The iodoacetate-injected rats develop electrically silent cramps in leg musculature during ischemic (or vigorous non-ischemic) exercise. Post-exercise rhabdomyolysis is evidenced by a 10-fold serum CPK elevation, excessive uptake of 99mTc-diphosphonate by cramped muscle, and type IIB fiber damage (histochemically-demonstrated) in cramped muscle. Further analysis of this model will allow a greater understanding of the clinical syndrome associated with the human disorders and permit development of successful treatment programs.

Contrary to common assumption, internal vascularization of muscle fiber occurs independent of muscle fiber splitting. Review of 1091 cases who underwent muscle biopsies demonstrated muscle fibers with internal blood vessels in a wide variety of chronic neuromuscular disease states, predominantly in patients with chronic neurogenic diseases. Many of these cases show evidence of internal disorganization or focal degeneration of muscle fibers, in particular, formation of targets, targetoids or similar structural alterations. Internal vascularization of muscle fiber probably occurs as a "healing" or "reparative process" in such fibers. Myopathic features, especially secondary myopathic changes (as seen in chronic denervation-reinnervation) are common and appear to be a necessary accompaniment of this phenomena. The vascularized muscle fiber is more likely to be seen in a distal lower extremity muscle than in a proximal limb muscle biopsy.

Some recently described abnormalities in the serum and red cell membranes in Duchenne dystrophy have been examined as methods of carrier detection in a single-blind controlled study. Twelve carriers (4 definite, 3 probable and 5 possible carriers previously found to have raised creatine kinase levels) and 12 normal female controls of the same age, were examined on 3 separate occasions at approximately two-weekly intervals. Analysis of age-dependent red cell shape changes, serum haemopexin levels, red cell K + efflux rate, sensitivity of red cell ghost membrane ATPase to ouabain, membrane protein phosphorylation studies and lactate dehydrogenase isoenzyme profiles on agarose gel electrophoresis all failed to distinguish carriers from controls. The carriers suffered muscle cramps more frequently than the controls and all but one carrier and two control subjects were correctly identified by manual muscle strength testing, certain proximal muscles in particular being consistently weaker in carriers than in the control group subjects. Scalar electrocardiography revealed higher values for the R/S ratio in Leads V 1 and V 2 and the sum (R–S) in V 2 .

An increasing number of cases of myopathy due to disordered lipid metabolism have recently been recognised and these appear to fall into two contrasting clinical and biochemical categories. Some patients present with steadily prograssive proximal weakness which sometimes responds to steroid therapy and which is due to carnitine deficiency in skeletal muscle. In the second category, patients usually present with muscle cramps on exertion then followed by myoglobinuria without established proximal myopathy and their symptoms are associated with deficiency of carnitine palmityl transferase in skeletal muscle. In this paper we report a patient who has well-documented carnitine palmityl transferase deficiency, whose symptoms were triggered by violent exercise after fasting and in whom there was variable histochemical and ultrastructural evidence of lipid accumulation in muscle biopsy samples. Development of the patient's symptoms was suppressed by a high carbohydrate diet.

The clinical, electrophysiological and muscle biopsy findings of 7 cases with a peculiar form of X-linked hereditary degenerative motor neuron disease are presented. It is suggested that the disease might be a separate clinical entity with the following characteristics: (1) sex-linked recessive inheritance, (2) unusual but not invariable late onset, (3) slow progression, (4) facial-bulbar and proximal spinal muscle involvement, (5) consistent fasciculations, sometimes massive and more pronounced about the lips, chin and tongue, (6) fine tremor of the hands, (7) muscle cramps usually preceding the other symptoms, and (8) gynaecomastia as a frequent but not a constant feature.

A case of McArdle 's syndrome in a 17-year-old male who suffered from muscle cramps and stiffness on moderate exertion is described. The diagnosis of McArdle 's syndrome was suggested by the demonstration that the blood lactate failed to rise following exercise and was confirmed by specialised techniques applied to a muscle biopsy. Light microscopy showed peripheral vacuoles in the muscle fibres. Histochemical methods showed an excess of glycogen in the periphery of the muscle fibres and absence of the muscle enzyme phosphorylase. Biochemical analysis of the muscle showed a 3-fold rise in glycogen and the phosphorylase assay gave a result of less than 10% of normal. Electron microscopy showed a gross excess of glycogen situated in the sub-sarcolemmal regions, between the muscle myofibrils and between the individual myofilaments. In the last-named situation the glycogen accumulation was related to the I band and was not seen in the A band. The significance of the clinical, histochemical, biochemical and ultrastructural findings is discussed and methods of diagnosis are suggested. The literature is briefly reviewed.

The clinical observation concerns a male patient of 46 years, who, after an infective disorder in 1946, showed fasciculation and painful cramps in the legs ceasing spontaneously in eight months. Ten years later, without obvious cause, fasciculations reappeared as well as painful cramps in the face and upper limbs. These cramps are set off by voluntary activity and almost immobilize the patient in a state of persisting painful contracture. In some muscles a distinct myotonic reaction could be obtained on mechanical tapping. Routine laboratory tests and neuro-chemical examinations failed to demonstrate any underlying metabolic disorder. Muscle-biopsy showed certain anomalies without obvious signs of myopathy or myositis, nor of neurogenic muscle-involvement. Repeated electromyography showed distinct characteristics of myotonia and of tetany. Nerve-block, as well as novocaine infiltration of the end-plate, showed the seat of abnormal electrical activity to be the motor end-plate or the muscle-fibre itself. The controlled action of various medications is discussed. All these measures remained ineffectual, with only a transient betterment, and the patient's condition progressively worsened by dint of an increasing and persistent contracture, especially in the lower limbs. A review is made of the literature of similar clinical cases.

Episodes with muscle ache, rhabdomyolysis and myoglobinuria with or without associated renal insufficiency are characteristic of muscle carnitine-palmitoyltransferase (CPT) deficiency. However, patients differ from each other in many aspects, such as the kind of stimulus that triggers rhabdomyolysis, the ability to produce ketone bodies when fasting, whether the enzyme defect is localized in skeletal muscle or is general, and the nature of the enzyme defect, which may be in CPT I or CPT II or both. Studies of muscle, liver and fibroblasts from a patient with recurrent rhabdomyolysis spontaneously occurring or triggered by exercise or fever, revealed a CPT deficiency in the muscle and liver biopsy samples but normal CPT activity in cultured cells, differing from previously reported patients. The enzyme defect in muscle was evidenced by two different methods, but not when determined with a method that measures the formation of palmitoylcarnitine. The enzyme abnormality in the patient's liver was associated with a delayed ketone body production and with a dramatic increase in long-chain acylcarnitines in the serum when fasting. Moreover the patient was unable to build up ketones when fed long-chain triglycerides (LCT) but showed prompt ketogenic response when fed medium-chain triglycerides (MCT). The heterogeneity of clinical presentations and of the biochemical findings in patients with CPT deficiency are discussed.

Two sisters presented with progressive muscle cramps, as well as wasting and weakness of the legs with onset after age 20. They also showed intention tremor of the upper extremities and dysarthria starting during the first decade. The older patient also had fasciculations; the younger, hyperreflexia. Total plasma beta-hexosaminidase (Hex) activity with 4-methylumbelliferyl-acetyl-glucosamine as substrate was reduced to 1.4% and 2.7% of the control in the 2 patients, respectively. Hex A activity measured by 4-methylumbelliferyl-N-acetylglucosamine-6-O-sulphate as substrate was 9.9% and 12.8% of the mean control value in the 2 patients, respectively. Hex B activity was undetectable in both patients. Leukocyte total Hex activity was 7-8% of normal; residual Hex A activity in the 2 patients was 17.8% and 16.3% of normal controls, respectively. Fibroblastic residual Hex A activity in the 2 patients was 9.6% and 22% of normal mean value, respectively. Appendiceal ganglion cells contained membranous cytoplasmic bodies in the younger patient. Thin layer chromatography of the appendiceal extract from one patient (III/2) showed a marked increase of GM2 ganglioside, and some increase of GM3 ganglioside. Northern blots performed on fibroblast cell lines from both patients for the demonstration of alpha and beta locus messenger RNA showed no difference between patients and control. These patients have a rare form of adult-onset progressive motor neuron disease presumably due to abnormal beta subunits, causing severe deficiency of both Hex A and Hex B. The phenotypic expression of this disease is similar to motor neuron disease due to alpha locus mutations, which suggests that the Hex A deficiency, even though only a partial one, may be the important pathogenic factor.

A family with adult spinal and bulbar muscular atrophy with X-linked recessive inheritance (Kennedy's disease) is described. Affected members presented at age 20 with muscle cramps followed insidiously by gynaecomastia, partial loss of secondary sexual traits, loss of libido and inability to maintain an erection. Three had also testicular atrophy and severe oligospermia was found in two patients. Testicular biopsy in one case showed germinal failure with almost normal Leydig cells. Hormonal tests were suggestive of a primary testicular failure. Etiologic possibilities are considered.

AMP deaminase activity was undetectable by a sensitive spectrophotometric assay in the muscle biopsy of a 37-year-old man with gout and exercise-related cramps and myalgia. Venous ammonia failed to rise after ischemic exercise, but the diagnostic value of this test is uncertain because changes of plasma ammonia after exercise varied greatly in different normal individuals. In the patient, AMP deaminase activity was normal not only in erythrocytes, leukocytes and cultured fibroblasts but also in muscle cultures. Presence of AMP deaminase in muscle cultures was probably due to the expression of a fetal isoenzyme under separate genetic control from adult muscle AMP deaminase.

The clinical, electrophysiological and muscle biopsy findings of 7 cases with a peculiar form of X-linked hereditary degenerative motor neuron disease are presented. It is suggested that the disease might be a separate clinical entity with the following characteristics: (1) sex-linked recessive inheritance, (2) unusual but not invariable late onset, (3) slow progression, (4) facial-bulbar and proximal spinal muscle involvement, (5) consistent fasciculations, sometimes massive and more pronounced about the lips, chin and tongue, (6) fine tremor of the hands, (7) muscle cramps usually preceding the other symptoms, and (8) gynaecomastia as a frequent but not a constant feature.

A syndrome is described consisting of the following symptoms and signs: hemifacial spasm (unilateral or bilateral and combined with weakness of the facial muscles), optic atrophy, pupillary changes of the Argyll Robertson type, a disturbance of the movements of the eyes without diplopia, reduced caloric reactions, slight to moderate peripheral paresis in the legs, diminished or absent tendon reflexes, reduced motor conduction velocity in the peripheral nerves, foot deformity of the Friedreich type, and trophic ulcers on the feet. Some of the symptoms and signs seem to appear at a pre-school age or nearly adult life. The disease is slowly progressive. The main symptoms are known to have been present for six generations in one single family, which immigrated to Sweden in the 17th century from an area now situated in Belgium. The hereditary trait is dominant. The syndrome seems to be a unique clinical entity, from a clinical and neurophysiological point of view belonging to the group of hereditary polyneuropathies. The underlying cause is unknown. No causal therapy exists but the facial hemispasm seems to respond well to treatment with carbamazepine (Tegretol) .