Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis.

BACKGROUND AND PURPOSE: Tapering immunosuppressants is desirable in patients with well-controlled myasthenia gravis (MG). However, the association between tapering of calcineurin inhibitor dosage and reduction-associated exacerbation is not known. The aim of this study was to clarify the frequency of reduction-associated exacerbation when tacrolimus is tapered in stable patients with anti-acetylcholine receptor antibody-positive MG, and to determine the factors that predict exacerbations. METHODS: We retrospectively analyzed 115 patients in whom tacrolimus dosage was tapered. The reduction-associated exacerbation was defined as the appearance or worsening of one or more MG symptoms <3 months after the reduction. RESULTS: Tacrolimus dosage was successfully tapered in 110 patients (96%) without any exacerbation. Five patients (4%) experienced an exacerbation, but symptoms were reversed in all patients when the tacrolimus dose was increased to the previous maintenance level. No patient developed an MG crisis. The age at onset was significantly earlier (30 vs. 56 years, P = 0.025) and the reduction in dosage was significantly larger (2.0 vs. 1.0 mg/day, P = 0.002) in patients with reduction-associated exacerbation than in those without exacerbation. The cut-off values determined in a receiver-operating characteristic curve analysis were 52 years (sensitivity, 57%; specificity, 100%) for the age at onset and 1.5 mg (sensitivity, 80%; specificity, 100%) for the dose reduction. CONCLUSION: Tapering of tacrolimus was possible in most patients with well-controlled anti-acetylcholine receptor antibody-positive MG. Early age at onset and a large reduction from maintenance dosage were associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late-onset disease.

Sudden onset of sleep due to hypothalamic lesions in neuromyelitis optica spectrum disorder positive for anti-aquaporin-4 antibody.

We report a patient with neuromyelitis optica spectrum disorders who presented with sudden onset of sleep as the sole manifestation. Magnetic resonance imaging investigation revealed lesions in the hypothalamus bilaterally, which vanished completely after methylprednisolone pulse therapy.

Spread of the radial SNAP: a pitfall in the diagnosis of carpal tunnel syndrome using standard orthodromic sensory conduction study.

OBJECTIVE: To investigate the occurrence of the spread of the radial sensory nerve action potential (SNAP) among patients with carpal tunnel syndrome (CTS) during standard median orthodromic sensory conduction study (SCS) using index finger stimulation. METHODS: We prospectively examined 74 hands in 56 CTS patients. We stimulated the index finger using ring electrodes. SNAPs were recorded at wrist over median and radial nerves. RESULTS: A spread of radial SNAP was clearly identified over the median nerve despite its small amplitude, in 72/74 hands during stimulation of the base of the index finger. In hands with delayed median SNAP, two peaks were observed; however in hands with absence of genuine median SNAP, only one peak of the spread was noticed. The proximal interphalangeal joint (PIP) stimulation still elicited an identifiable spread in 47/74 hands. CONCLUSION: This spread phenomenon is a previously undescribed pitfall during the standard median orthodromic SCS, frequently occurring in CTS patients. SIGNIFICANCE: In severe CTS cases, one may make wrong conclusion of normal median sensory latency if unaware of this pitfall.

N10 component in median nerve somatosensory evoked potentials (SEPs) is not an antidromic motor potential.

OBJECTIVE: To test the hypothesis that the N10 far-field potential in median nerve somatosensory evoked potentials is generated by the motor axons by examining patients with amyotrophic lateral sclerosis (ALS). METHODS: Subjects were 5 ALS patients showing pronounced or complete denervation of median-innervated small hand muscles. We evaluated N10 over scalp, and proximal plexus volleys (PPVs) at lateral or anterior cervical electrode. RESULTS: N10 and PPVs were definitely preserved for every ALS subject. N10 amplitudes of ALS subjects were even significantly larger than control subjects. In one ALS patient completely lacking motor axons, N10 was larger than the largest one among control subjects. CONCLUSIONS: Present results clearly indicate that N10 is not predominantly generated by motor axons but by the whole median nerve dominated by sensory axons. We propose a theory that N10 is a junctional potential generated by the entrance of the median nerve into bone at the intervertebral foramen, producing a positive pole at the non-cephalic reference electrode. Significantly larger N10 in ALS subjects may be due to the lack of cancellation by slower motor axons. SIGNIFICANCE: The hypothesis that N10 is generated by motor axons is refuted, and a new theory of its generation is presented.

Single fiber EMG and repetitive nerve stimulation of the same extensor digitorum communis muscle in myasthenia gravis.

OBJECTIVE: To compare voluntary single fiber electromyography (v-SFEMG) and repetitive nerve stimulation (RNS) at the same extensor digitorum communis (EDC) muscle in myasthenia gravis (MG). METHODS: We examined v-SFEMG and RNS successively on the same day in the same EDC muscle. We studied 45 examinations of both v-SFEMG and RNS in 29 patients suffering from MG, together with examinations of RNS in 30 control subjects. RESULTS: Forty-one of 45 (91%) v-SFEMGs showed abnormal results, whereas only 18/45 (40%) RNSs showed an abnormal decrement. The percentage of decrement showed similar correlations with 3 v-SFEMG parameters: percentage of abnormal pairs, percentage of blocking pairs, and the mean MCD value. Examinations showing a significant decrement in RNS had at least 60%, and usually no less than 90%, abnormal pairs, and 10-80% blocking pairs. Some muscles without a decrement had up to 50% blocking pairs. CONCLUSIONS: These results suggest that the blocking phenomenon observed in v-SFEMG is not a direct counterpart of the decrement in RNS. This must be partly because fibers contributing to the decrement are continuously blocked during voluntary contraction, and partly, because smaller motor units explored by v-SFEMG are probably more abnormal in MG than larger motor units mainly contributing to a decrement. Both factors make v-SFEMG much more sensitive than RNS.

Anatomic origin and clinical application of the widespread N18 potential in median nerve somatosensory evoked potentials.

N18 is a broad negativity, with a duration of approximately 20 msec after positive far-field potentials and is recorded widely over the scalp using a noncephalic reference. Its origin has been controversial but its preservation after pontine or upper medullary lesion while loss after high cervical lesions suggested its medullary origin. Comparison with animal studies and direct recording studies in humans leads the authors to conclude that N18 is most likely generated at the cuneate nucleus by primary afferent depolarization. Namely, dorsal column afferents send collaterals to interneurons within the cuneate nucleus, which in turn synapse on presynaptic terminals of dorsal column fibers and depolarize them as a mechanism of presynaptic inhibition. In this way, an electrical sink is formed on presynaptic terminals, whereas their dorsocaudally situated axons serve as a source. The ventrorostral negative pole of the resultant dipolar potential must correspond to N18. The authors obtained a measure to evaluate medullary function objectively, and therefore N18 may be useful as a diagnostic tool for brain death. Usage of a C2S reference is essential for the accurate estimation of N18. Origins of other somatosensory evoked potential components related to the cuneate nucleus are also discussed.

Lower cervical origin of the P13-like potential in median SSEPS.

The authors studied the origin of the scalp P13-like potential in median somatosensory evoked potentials, which have been reported to be preserved in patients with cervicomedullary lesions or in brain death. There were five patients with high to middle cervical lesions (C2/3 or C3/4 level). Small P13-like potentials after P11 were identified for all patients with a noncephalic reference but not with an ear reference. Their onset latencies were slightly earlier than the expected latency of the true P13/14 onset. In two patients, delayed true P13/14s followed by N18s were identified with both noncephalic and ear references. The authors argue that the P13-like potential observed in these patients is a different entity from scalp P13 in normal subjects. Because the C3/4 vertebral level corresponds to the C5 cord level, the origin of the P13-like potential must be below C5, contradicting the previous opinion that it is generated at the cervicomedullary junction or at the high cervical dorsal column. The authors named this potential lower cervical P13 (or lcP13), and present an opinion that it is generated by the beginning of the second spinal ascending volley, which has been described by direct-recording studies in humans.

[Diagnostic criteria of conduction block and the spectrum of diseases which is accompanied with conduction block].

To establish the criteria of conduction block is essential for its clinical application. Nerve conduction studies were performed on 15 normal controls. Peak-to-peak amplitude, negative wave area and negative wave duration were measured and their ratios between proximal and distal stimulation were estimated. The results were summarized in Table. Decrease of amplitude and area was the more conspicuous in the longer segment, and therefore it was suspected to be due to the duration-dependent phase cancellation. Since area reduction was less than the amplitude reduction, the area was a more useful parameter than the amplitude. The importance to provide different normal values for the different nerve segment was emphasized. The diseases which are known to be accompanied with conduction block include AIDP, CIDP and entrapment neuropathy. Multifocal motor neuropathy with conduction block associated with anti-GM1 antibody is recently noticed and we presented the cases we experienced. By contrast, it has been demonstrated that HMSN type 1 does not show conduction block. We examined diabetic and uremic neuropathies and showed that they do not have conduction block. These facts suggest that the demyelination does not always produce conduction block.

[Readiness potential associated with an athetotic movement].

A 28-year-old man was admitted to our hospital because of focal seizures probably generated by the right sensorimotor cortex with secondary generalization for 3 months. He had 5 years history of keratoconjunctivitis and iriditis. Physical examination revealed minimal hemiparesis and hyperreflexia in the left side and left papillitis. Cerebrospinal fluid analysis showed 75 cells per cubic-millimeter (all lymphocytes) and 88 mg/dl protein. Computerized tomography of the brain revealed elimination of the sulcus and vague enhancement of the cortex in the right cerebral hemisphere. The symptoms and the laboratory data improved spontaneously in a few months. Slow, athetotic movements were observed in the left forearm extensor muscles for about 10 days period. Electromyography (EMG) of these movements showed bursts of 300-800 sec in duration which repeated almost regularly at a varying frequency of 0.3-0.5 msec. The electroencephalographic (EEG) studies revealed slow background activities over the right hemisphere. The simultaneous recording of EEGs and EMGs demonstrated no EEG activity correlated with the athetotic movements. In the jerk-locked averaging (JLA) recorded with the time constant of 0.3 sec, no spiky or sharp EEG activities were detected before the EMG discharges of the left forearm extensor muscles. However, JLA with the time constant of 3.2 sec disclosed a slow negative shift which preceded the athetotic movement by about 500 msec. This negative potential was fairly localized in the right central area, which was thought to be consistent with the hand area of the motor cortex contralateral to the muscles showing the athetotic movements. The present case had a wide-spread, mainly unilateral lesion in the cerebral hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS)

[Motor-dominant neuropathy with multifocal conduction block].

Patient 1 was a 39-year-old man; patient 2, a 42-year-old woman; patient 3, a 78-year-old man. Leading symptoms were chronic asymmetrical weakness in all three cases, which started in a distal portion of the upper extremities. Muscle atrophy was often less prominent than would be expected from the power of the muscle. Fasciculations were observed in two patients and the initial symptom of patient 2 was painful cramp of the right thumb. Patient 1 initially had mild transient dysesthesia of the right fingers. The other two patients had no sensory symptoms or signs. General laboratory tests revealed no particular abnormalities except that patient 3 had mild diabetes mellitus, although the type of neuropathy in patient 3 was quite different from diabetic neuropathy. Total protein concentrations in the cerebrospinal fluid were 34, 32 and 43 mg/dl in three patients, respectively (normally, less than 40 mg/dl). Motor nerve conduction studies revealed conduction block in more than one nerve in every case. Conduction velocities were generally normal in those segments of nerve where conduction block was not detected. Serum anti-ganglioside antibodies were investigated by Enzyme-linked immunosorbent assay (ELISA). Glycolipids used as the antigen include GM1, GM2, GM3, GD1b, GD3, GT1b, GQ1b, GA1 and galactocerebroside. Strong IgM antibody activity against GM1, GD1b and GA1 was noted in patient 1. Weaker but significant IgM antibody activities against GM1 and GA1 were detected in patient 2 and 3. Thin-layer chromatography immunostaining also confirmed these results. Muscle biopsy in patient 1 revealed a lot of target fibers and profuse polyglucosan bodies in the axons of intramuscular nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of left subclavian artery occlusion with transient ischemic attacks probably in the internal carotid artery system].

The subclavian steal syndrome is known to steal blood flow from the vertebrobasilar system. However, we experienced a case of subclavian artery occlusion presenting transient ischemic attacks in left internal carotid system. A left handed 41-year-old man developed transient dysarthria and right hemiparesis including face several times when he physically used his arms. He had no symptoms of the vertebrobasilar system. A brain MRI revealed an old cerebral lacuna at the left putamen supplied by perforating arteries of the middle cerebral artery. The angiography demonstrated a complete occlusion of the proximal portion of the left subclavian artery without a reverse flow from the vertebral artery. Instead, descending cervical branches and deep cervical branches of the ipsilateral external carotid artery supplied collateral pathways to the occluded subclavian artery. On the basis of above observations, we speculated that he developed symptoms of the internal carotid system due to the steal through the collateral network of the cervical arteries directed to the subclavian artery. We should consider not only the vertebrobasilar system but also the internal carotid system, especially its cervical artery network, when exploring collateral pathways for the subclavian steal syndrome.

[Mono-radiculopathy multiplex--multiple infarction of the cauda equina caused by intravascular lymphomatosis].

A 55-year-old man had felt numbness of the bilateral peroneal sides of legs for 6 months. Then hepatosplenomegaly, anemia, body weight loss and fever developed, and a diagnosis of malignant histiocytosis (MH) was made by revealing the presence of innumerable atypical histiocytes with hemophagocytosis in the bone marrow. Soon later, sensory disturbance of bilateral peroneal sides of legs (right side dominant) developed and aggravated with painful dysesthesia and weakness of the legs for the last 2 weeks before death. Electrophysiologically, sensory conduction velocity of the sural nerve was normal and somatosensory evoked potentials from tibial nerve were normal before P15 but were not evoked at all after the lumbar potential, suggesting lumbosacral radiculopathy. Autopsy showed multifocal ischemic lesions and secondary degeneration of the lumbosacral nerve roots associated with necrosis and fibrosis of the radicular vessels and intravascular infiltration of atypical mononuclear cells which were positive for B cell markers. The neurological manifestations and the distribution of ischemic lesions, which were similar to those of vasculopathic mononeuropathy multiplex, would deserve the name of "monoradiculopathy multiplex".

[Dystrophin abnormality in a patient with polymyositis associated with primary biliary cirrhosis and myocardial injury].

We have reported a 58-year-old Japanese female with polymyositis, primary biliary cirrhosis (PBC) and arrhythmia. In contrast to the previously reported 13 cases of polymyositis associated with PBC, symptoms and laboratory data abnormalities responded to oral administration of predonisolone. Interestingly, immunohistochemical and immunoblot analyses of biopsied skeletal muscle revealed diminished expression of dystrophin carboxyl-terminal domain in the sarcolemma, suggesting that, in analogy to Duchenne muscular dystrophy, secondary abnormality of the link between the basal lamina and cytoskeleton via the dystrophinglycoprotein complex may have played a role in the molecular pathogenesis of muscle fiber degeneration in this patient.