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.

GM1/GalNAc-GD1a complex: a target for pure motor Guillain-Barre syndrome.

BACKGROUND: GM1 and GalNAc-GD1a are located on the axolemma of the motor nerves and are believed to be the antigens associated with pure motor Guillain-Barré syndrome (GBS). Furthermore, GM1 and GalNAc-GD1a may exist nearby and colocalize on the axolemma. Ganglioside complex (GSC) antigens associated with GM1 or GalNAc-GD1a can be target antigens in pure motor GBS. We investigated GBS sera for antibodies to a GSC consisting of GM1 and GalNAc-GD1a (GM1/GalNAc-GD1a) and analyzed the clinical and electrophysiologic findings of patients with antibodies to GM1/GalNAc-GD1a. METHODS: Sera from 224 patients with GBS were surveyed for antibodies to GSCs consisting of two of nine gangliosides (GM1, GM2, GM3, GD1a, GD3, GT1a, GT1b, GQ1b, and GalNAc-GD1a). We analyzed the clinical and electrophysiologic features of patients with IgG antibodies to the GM1/GalNAc-GD1a complex. RESULTS: Ten patients with GBS had IgG antibodies to the GM1/GalNAc-GD1a complex. The clinical findings of the 10 patients with GBS were characterized by preserved sensory system and infrequent cranial nerve deficits. According to the criteria established by Hadden et al., electrodiagnostic studies showed a demyelinating pattern in four patients and axonal neuropathy pattern in two. Early motor conduction block at intermediate nerve segments was found in five patients. CONCLUSIONS: GM1 and GalNAc-GD1a may form a complex in the axolemma at nodes of Ranvier or paranodes of the motor nerves, and may be a target antigen in pure motor Guillain-Barré syndrome, especially in the form of acute motor conduction block neuropathy.

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.

Reduced amplitude of the sural nerve sensory action potential in PARK2 patients.

The authors performed nerve conduction studies in nine PARK2 and eight idiopathic Parkinson disease patients and found a significant reduction of sural sensory nerve action potential (SNAP) amplitude in eight PARK2 patients who mostly remained asymptomatic. These data suggest that sensory axonal neuropathy may be a common clinical feature of PARK2 and a reduced amplitude of sural SNAP could be a diagnostic indicator of PARK2.

New and reliable MRI diagnosis for progressive supranuclear palsy.

OBJECTIVE: To evaluate the area of the midbrain and pons on mid-sagittal MRI in patients with progressive supranuclear palsy (PSP), Parkinson disease (PD), and multiple-system atrophy of the Parkinson type (MSA-P), compare these appearances and values with those of normal control subjects, and establish diagnostic MRI criteria for the diagnosis of PSP. METHODS: The authors prospectively studied MRI of 21 patients with PSP, 23 patients with PD, 25 patients with MSA-P, and 31 age-matched normal control subjects. The areas of the midbrain tegmentum and the pons were measured on mid-sagittal MRI using the display tools of a workstation. The ratio of the area of the midbrain to the area of the pons was also evaluated in all subjects. RESULTS: The average midbrain area of the patients with PSP (56.0 mm2) was significantly smaller than that of the patients with PD (103.0 mm2) and MSA-P (97.2 mm2) and that of the age-matched control group (117.7 mm2). The values of the area of the midbrain showed no overlap between patients with PSP and patients with PD or normal control subjects. However, patients with MSA-P showed some overlap of the values of individual areas with values from patients with PSP. The ratio of the area of the midbrain to the area of pons in the patients with PSP (0.124) was significantly smaller than that in those with PD (0.208) and MSA-P (0.266) and in normal control subjects (0.237). Use of the ratio allowed differentiation between the PSP group and the MSA-P group. CONCLUSION: The area of the midbrain on mid-sagittal MRI can differentiate PSP from PD, MSA-P, and normal aging.

Tibial nerve SEPs localized the lesion site in a patient with early tabes dorsalis.

There is controversy regarding the initial pathology of tabes dorsalis. In a patient with early tabes dorsalis, tibial nerve somatosensory evoked potentials elicited normal P15, a delayed traveling peak in the lumbar bipolar leads, and absent subsequent components. Based on the comparison with normative data and stimulation at different intensities, the authors conclude that only the slower conducting antidromic motor volleys are preserved, whereas the dorsal root is damaged at its distal end.

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.

Abductor sign: a reliable new sign to detect unilateral non-organic paresis of the lower limb.

OBJECTIVES: To test a new neurological sign, the "abductor sign," which can distinguish between organic and non-organic leg paresis using synergic movements of the bilateral hip abductors. METHODS: The subjects were 33 patients presenting with paresis of one leg, 17 of organic origin and 16 of non-organic origin (hysteria). To test the abductor sign, the examiner told the patient to abduct each leg, and opposed this movement with his hands placed on the lateral surfaces of the patient's legs. The leg contralateral to the abducted one showed opposite actions for organic paresis and non-organic paresis: for example, when the paretic leg was abducted, the sound leg stayed fixed in organic paresis, but moved in the hyperadducting direction in non-organic paresis. Hoover's sign was used for comparison in the same patients. RESULTS: The abductor sign gave the correct classification for all 33 cases. Hoover's sign was reliable if the results were carefully interpreted, but it was non-diagnostic for 16 patients because of strong hip extensors and in two because of strong hip flexors. Two patients with non-organic paresis succeeded in tricking the examiner by pretending full effort to lift the paretic leg. CONCLUSIONS: The abductor sign is a useful test to detect non-organic paresis, because (1) it is difficult for a hysterical patient to deceive the examiner, (2) the hip abductor is one of the most commonly involved muscles in pyramidal weakness, and (3) the results are easily visible as movement or non-movement of the unabducted leg.

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.

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.