Sporadic case of spinocerebellar ataxia type 17: treatment observations for managing urinary and psychotic symptoms.
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Anticonvulsants↗
Biomedical subjects
Satoshi Kuwabara
Publications and source records attributed to Satoshi Kuwabara.
Urinary retention and sympathetic sphincter obstruction in axonal Guillain-Barré syndrome.
A 62-year-old woman with axonal Guillain-Barré syndrome developed weakness and urinary retention simultaneously. The retention failed to recover for 10 months even after she regained the ability to walk. The patient exhibited no postural hypotension. Videourodynamics showed that the retention was caused not by the bladder paralysis but rather by internal (sympathetic) sphincter obstruction, which is extremely uncommon in peripheral neuropathies. We started the patient on an alpha-adrenergic antagonist, urapidil, at 30 mg/day, and this led to successful relaxation of the urethra and reduced the postvoid residual from 200 ml to less than 30 ml. The underlying mechanisms of urinary retention in our patient appeared to involve hyperactive lumbosacral sympathetic nerves. Urinary retention and sympathetic sphincter obstruction can thus be features of axonal Guillain-Barré syndrome.
Adrenergic alpha-Antagonists↗
Time course of axonal regeneration in acute motor axonal neuropathy.
Patients with acute motor axonal neuropathy (AMAN) generally recover well. We reviewed clinical and electrophysiologic recovery in 13 patients for up to 5 years. Twelve patients showed rapid recovery over 12 months, whereas in the remaining one the recovery was slow and incomplete at 5 years. In AMAN, axonal degeneration appears to develop predominantly in the motor nerve terminals, and only occasionally more proximally in the nerve roots. Nerve terminal degeneration-regeneration presumably provides a mechanism for good recovery.
Adolescent↗
Guillain-barré syndrome.
Guillain-Barré syndrome (GBS) is currently divided into the two major subtypes: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). This review highlights relevant recent publications, particularly on the pathophysiology of AMAN. Molecular mimicry of the bacterial lipo-oligosaccharide by the human gangliosides is now considered an important cause of AMAN. Gangliosides GM1, GM1b, GD1a, and GalNAc-GD1a expressed on the motor axolemma are likely to be the epitopes for antibodies in AMAN. At the nodes or paranodes, deposition of antiganglioside antibodies initially cause reversible conduction block followed by axonal degeneration. Electrodiagnostic findings support this process. Disruption of glycolipids, which are important to maintain ion channel clustering at the nodes and paranode, may impair nerve conduction. Genetic polymorphisms of Campylobacter jejuni determine the expression of the gangliosides on the bacterial wall. In contrast, target molecules in AIDP have not yet been identified. Meta-analyses show efficacy of plasmapheresis and immunoglobulin therapy, but not corticosteroids, in hastening recovery.
Guillain-Barre Syndrome↗
The effects of physiological fluctuation of serum potassium levels on excitability properties in healthy human motor axons.
OBJECTIVE: Previous axonal excitability studies suggest hyperkalemia or hypokalemia can significantly alter membrane potential and thereby, excitability properties. We studied whether physiological fluctuation of serum potassium levels affects axonal excitability in normal human axons. METHODS: Threshold tracking was used to measure strength-duration properties, refractory periods, supernormality, and threshold electrotonus in median motor axons of 12 normal volunteers. In each subject, the excitability indices and serum potassium levels were measured three times (baseline, 2h later, and 2 weeks later). RESULTS: The pooled data (n=36) showed significant correlation of the relative refractory period, supernormality, and depolarizing threshold electrotonus with potassium levels. Among each trial (12 subjects) the correlation did not reach statistical significance occasionally. Strength-duration properties, refractoriness, late subnormality, and hyperpolarizing threshold electrotonus were not significantly affected by serum potassium levels. CONCLUSIONS: Even in the normal range, serum potassium levels could slightly alter axonal excitability of human axons. Among excitability indices, the relative refractory period, supernormality, and threshold electrotonus are sensitive to potassium levels. SIGNIFICANCE: Physiological fluctuation of serum potassium levels could partly be responsible for inter- and intra-subject variability of excitability indices.
Adult↗
Increased nodal persistent Na+ currents in human neuropathy and motor neuron disease estimated by latent addition.
OBJECTIVE: To investigate the changes in nodal persistent Na(+) currents in human neuropathy and motor neuron disease. In human motor axons, approximately 1.0% of total Na(+) channels are active at rest, termed "persistent" Na(+) channels, and the conductance can be non-invasively estimated by the technique of latent addition in vivo. METHODS: Latent addition was performed in median motor axons of 93 patients with axonal neuropathy (n=38), lower motor neuron disorder (LMND; n=19) or amyotrophic lateral sclerosis (ALS; n=36) and in 27 age-matched normal subjects. Brief hyperpolarizing conditioning current pulses were delivered, and threshold change at the conditioning-test interval of 0.2 ms was measured as an estimator of the magnitude of persistent Na(+) currents. Threshold electrotonus and supernormality were also measured as indicators of resting membrane potential. RESULTS: Threshold changes at 0.2 ms were significantly greater in patients with neuropathy or LMND (p<0.05), and tended to be greater in ALS patients (p=0.075) than in normal controls. Threshold electrotonus and supernormality did not differ in each patient group and normal controls, suggesting that membrane potential is not altered in patients. In the recovery phase of axonal neuropathy, the threshold changes increased in parallel with an increase in amplitudes of compound muscle action potential. CONCLUSIONS: Persistent Na(+) currents appear to increase commonly in disorders involving lower motor neurons, possibly associated with axonal regeneration or collateral sprouting or changes in Na(+) channel gating. SIGNIFICANCE: The increased axonal excitability could partly be responsible for positive motor symptoms such as muscle cramping frequently seen in lower motor neuron disorders.
Action Potentials↗
Chronic inflammatory demyelinating polyneuropathy associated with idiopathic hemochromatosis.
We describe a 50-year-old woman who developed chronic inflammatory demyelinating polyneuropathy (CIDP) one year after onset of hemochromatosis. Electrodiagnostic studies showed evidence of multifocal demyelination. Marked hypergammaglobulinemia with positive anti-nuclear and anti-DNA antibodies was found. Corticosteroid treatment resulted in a significant lessening of neurological symptoms. This is the first case of CIDP with hemochromatosis. The association may be coincidental, but the altered immune system by hemochromatosis was possibly related to the development of CIDP in this patient.
Adrenal Cortex Hormones↗
Distal excitability changes in motor axons in amyotrophic lateral sclerosis.
OBJECTIVE: Previous axonal excitability studies in amyotrophic lateral sclerosis (ALS) have suggested that impaired potassium channel function could be responsible for the generation of fasciculations, but the ectopic activity arises predominantly from the motor nerve terminals. This study tested the hypothesis that dysfunction of potassium channels is more pronounced in the more distal parts of axons. METHODS: Threshold electrotonus was used to compare accommodation at the motor point of abductor pollicis brevis, and at the wrist portion of the median nerve, between 22 patients with ALS and 19 normal subjects. As target responses for motor point stimulation, movement-related potentials were recorded using an accelerometer. RESULTS: Compared to normal subjects, ALS patients showed greater threshold changes to depolarizing conditioning currents at both the motor point and wrist, suggesting less accommodation by potassium currents. Differences in the threshold electrotonus curves between the normal and ALS groups were much more prominent at the motor point than at the wrist. CONCLUSIONS: In ALS, axonal potassium channels are impaired more prominently in distal portions of axons than at the nerve trunk, and this is consistent with evidence that fasciculations mostly arise from the nerve terminals. SIGNIFICANCE: Excitability testing at the motor point provides additional information about the pathophysiology of ALS.
Action Potentials↗
Latent addition in human motor and sensory axons: different site-dependent changes across the carpal tunnel related to persistent Na+ currents.
OBJECTIVE: To compare site-dependent changes across the carpal tunnel in axonal persistent Na+ conductances in motor and sensory axons. Positive sensory symptoms are prominent features in carpal tunnel syndrome, and a persistent Na+ current is a major determinant of axonal excitability. METHODS: The technique of latent addition was used to estimate persistent Na+ currents in median motor and sensory axons at the wrist and palm of 10 normal subjects. Brief hyperpolarizing conditioning current pulses were delivered, and threshold change at the conditioning-test interval of 0.2 ms was measured as an indicator of persistent Na+ currents. RESULTS: Threshold changes at 0.2 ms were greater in sensory than in motor axons at both the wrist and palm. In motor axons, the threshold changes were significantly smaller at the palm (mean, 4.9%) than at the wrist (10.0%). By contrast, the threshold changes were similar at the two sites of sensory axons (12.6 and 13.1%). The passive membrane time constant was similar for motor and sensory axons at the palm and wrist. CONCLUSIONS: Nodal persistent Na+ conductances have substantial site-dependent changes decreasing distally across the carpal tunnel in median motor axons, but not in sensory axons. SIGNIFICANCE: Whereas sensory axons generally have higher excitability than motor axons, the sensory-motor differences become more prominent across, and possibly at the carpal tunnel than the nerve trunk, and it is suggested that this contributes to the predominance of positive sensory symptoms in carpal tunnel syndrome.
Action Potentials↗
Nodal persistent Na+ currents in human diabetic nerves estimated by the technique of latent addition.
OBJECTIVE: To investigate the effects of hyperglycemia on persistent Na+ currents in human diabetic nerves, eliminating the factors of passive membrane properties as a factor. Previous studies show that strength-duration time constant of a nerve is shortened under hyperglycemia, suggesting reduced axonal persistent Na+ currents. However, the time constant is also affected by changes in passive membrane properties. Latent addition using computerized threshold tracking is a new method that can separately evaluate Na+ currents and passive membrane properties. METHODS: Latent addition was used to estimate nodal Na+ currents in median motor axons of 83 diabetic patients. Brief hyperpolarizing conditioning current pulses were delivered, and threshold changes at the conditioning-test interval of 0.2 ms were measured as an indicator of nodal persistent Na+ currents. Seventeen patients were examined before and after insulin treatment. RESULTS: There was an inverse linear relationship between hemoglobin A1c levels and threshold changes at 0.2 ms (P=0.02); the higher hemoglobin A1c levels were associated with smaller threshold changes. After insulin treatment, there was a significant improvement in nerve conduction velocities associated with greater threshold changes at 0.2 ms (P=0.03), suggesting an increase in persistent Na+ currents. The fast component of latent addition, an indicator of passive membrane properties, was not affected by the state of glycemic control. CONCLUSIONS: Hyperglycemia could suppress nodal persistent Na+ currents, presumably because of reduced trans-axonal Na+ gradient or impaired Na+ channels, and this can be rapidly restored by glycemic control. SIGNIFICANCE: Reduced nodal Na+ currents may partly contribute to the pathophysiology of human diabetic neuropathy.
Action Potentials↗
Altered axonal excitability properties in amyotrophic lateral sclerosis: impaired potassium channel function related to disease stage.
Fasciculations are a characteristic feature of amyotrophic lateral sclerosis (ALS), and can arise proximally or distally in the motor neuron, indicating a widespread disturbance in membrane excitability. Previous studies of axonal excitability properties (i.e. threshold electrotonus, strength-duration time constant) have suggested respectively that change in potassium or sodium channels may be involved. To reinvestigate these changes and explore their correlation with disease stage, multiple axonal excitability properties (threshold electrotonus, strength-duration time constant, recovery cycle and current-threshold relationship) were measured for the median nerve at the wrist in 58 ALS patients, and compared with 25 age-matched controls. In ALS, there were greater changes in depolarizing threshold electrotonus (i.e. less accommodation) (P < 0.001) and greater supernormality in the recovery cycles (P < 0.001). These abnormalities were more prominent in patients with moderately reduced CMAP (1-5 mV). Modelling the excitability changes in this group supported the hypothesis that axonal potassium conductances are reduced, resulting in increased supernormality despite membrane depolarization. The tendency for strength-duration time constant to be prolonged in ALS was only significant for patients with normal CMAP amplitude (>5 mV). Patients with severely reduced CMAP (<1 mV) alone showed reduced threshold changes to hyperpolarizing current. These results suggest a changing pattern of abnormal membrane properties with disease progression. First, persistent Na+ conductance increases, possibly associated with collateral sprouting, and then K(+) conductances decline. Both changes cause axonal hyperexcitability, and may contribute to the generation of fasciculations. These serial changes in axonal properties could provide insights into the pathophysiology of ALS, and implications for future therapeutic options.
Adult↗
Electrophysiological subtypes and prognosis of childhood Guillain-Barré syndrome in Japan.
Guillain-Barré syndrome (GBS) is classified into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), but little is known about the incidence of the subtypes and the prognosis of childhood GBS. To elucidate the features and long-term prognosis, clinical and electrophysiological data for 31 Japanese GBS children were reviewed. By electrodiagnostic criteria, children were classified as having AIDP (35%) or AMAN (48%), or were unclassified (16%). The AMAN children invariably had normal sensory nerve potentials. Between the two groups, age, sex, and clinical disability did not differ significantly, but the AIDP children more frequently had cranial and sensory nerve involvement, and the AMAN children more frequently had preceding gastroenteritis. By 6 months after onset, all the AIDP and 80% of the AMAN children had regained the ability to walk; by 2 years, all but one of the AMAN children could walk. In Japanese childhood GBS, the proportion of AIDP and AMAN appears to be similar. Recovery is generally favorable in both subtypes, but some of the AMAN children experienced delayed recovery.
Action Potentials↗
Rho-kinase inhibition enhances axonal regeneration after peripheral nerve injury.
In injured adult neurons, the process of axonal regrowth and reestablishment of the neuronal function have to be activated. We assessed in this study whether RhoA, a key regulator of neurite elongation, is activated after injury to the peripheral nervous system. RhoA is activated in motoneurons but not in Schwann cells after mouse sciatic nerve injury. To examine whether the activation of RhoA and its effector, Rho-kinase, retards axon regeneration of injured motoneurons, we employed a Rho-kinase inhibitor, fasudil. Amplitudes of distally evoked compound muscle action potentials are increased significantly faster after axonal injury in mice treated with fasudil compared with controls. Histological analysis shows that fasudil treatment increases the number of regenerating axons with large diameter, suggesting that axon maturation is facilitated by Rho-kinase inhibition. In addition, fasudil does not suppress the myelination of regenerating axons. These findings suggest that RhoA/Rho-kinase may be a practical molecular target to enhance axonal regeneration in human peripheral neuropathies.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Bickerstaff brainstem encephalitis after heat stroke.
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Adult↗
Concomitant chronic inflammatory demyelinating polyneuropathy and myasthenia gravis following cytomegalovirus infection.
We describe a patient who concomitantly developed chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) following cytomegalovirus (CMV) infection. Whereas CIDP and MG presumably have different immunopathogeneses, a number of reports presented cases with CIDP and MG, some of which were concomitant cases. Several reports described association between CIDP or MG, and CMV infection, although the association is still a matter of controversy. This is the first report of patients with concomitant CIDP and MG following CMV infection. The association may be coincidental, but the possibility that CMV infection triggered development of both CIDP and MG simultaneously cannot be excluded.
Cytomegalovirus Infections↗
Low-frequency transcranial magnetic stimulation for epilepsia partialis continua due to cortical dysplasia.
The potential therapeutic role of repetitive transcranial magnetic stimulation (rTMS) in epilepsy has been increasingly recognized. We investigated the effects of low-frequency rTMS in a patient with epilepsia partialis continua (EPC) due to cortical dysplasia. A 31-year-old female patient experienced EPC in the right upper and lower extremities, which had lasted for 15 years without generalized seizures. MRI showed focal megaencephaly around the motor cortex suggestive of cortical dysplasia. A figure of eight magnetic coil was placed over the hand motor area, and 100 stimuli with an intensity at 90% of motor threshold were given at 0.5 Hz. Immediately after rTMS, EPC was nearly abolished. The effects had continued approximately for 2 months, and the second trial resulted in the similar effects and time-course. Low-frequency rTMS was safe and well tolerated in this patient. These findings support the concept that rTMS decreases cortical excitability, and may be an effective treatment for focal partial seizures.
Adult↗
Strength-duration properties and glycemic control in human diabetic motor nerves.
OBJECTIVE: To investigate the influences of hyperglycemia on axonal excitability in human diabetic nerves. Hyperglycemia results in decreased Na+-K+ pump function, presumably leading to intra-axonal Na+ accumulation and thereby, reduced Na+ currents. METHODS: The strength-duration time constant (tau(SD)), which partly depends on persistent Na+ conductance active at the resting membrane potential, was measured in median motor axons of 79 diabetic patients. The relationship of tau(SD) with the state of glycemic control (hemoglobin A1c [HbA1c] levels) was analyzed. RESULTS: The mean tau(SD) was longer for diabetic patients than for normal controls, but the difference was not significant. Among diabetic patients, the subgroup of patients with good glycemic control (HbA1c<7%) had significantly longer tau(SD) than the patient group with poor control (HbA1c>9%; P=0.04). The mean tau(SD) was longest at the HbA1c level of 5-6%, gradually decreasing and reaching a plateau around the HbA1c level of 9%. There was an inverse relationship between HbA1c levels and tau(SD), when the HbA1c levels ranged from 5 to 9% (P=0.04). CONCLUSIONS: In diabetic nerves, tau(SD) is generally longer than normal, but hyperglycemia is associated with paradoxically shortened tau(SD), because of a decrease in axonal persistent Na+ conductance, possibly related to reduced membranous Na+ gradient, tissue acidosis, or other metabolic factors. SIGNIFICANCE: Measurements of tau(SD) could provide a new insight into changes in ionic conductance in human diabetic nerves.
Adult↗
The acute effects of glycemic control on nerve conduction in human diabetics.
OBJECTIVE: To investigate acute changes in nerve conduction associated with glycemic control. In diabetes, nerve dysfunction can result from reversible metabolic factors associated with hyperglycemia, as well as structural changes. METHODS: Multiple nerve conduction parameters including F-wave latencies were measured in 47 diabetic patients with prominent hyperglycemia before and after intensive insulin treatment. RESULTS: Four weeks after the start of treatment, there was a significant improvement in minimal F-wave latencies of the median (P<0.001) and tibial (P<0.001) nerves, and in distal latencies (P=0.01) and sensory nerve conduction velocities (P<0.001) of the median nerves. Amplitudes of motor and sensory responses did not change significantly. These findings were similar for patients with type 1 (n=8) and those with type 2 (n=39) diabetes. Patients with poorer glycemic control or milder neuropathy tended to show greater changes after treatment. CONCLUSIONS: Glycemic control quickly alters the speed of nerve conduction. F-wave latencies and conduction times across the carpal tunnel are very sensitive parameters. SIGNIFICANCE: Serial nerve conduction studies can detect reversible slowing of nerve conduction presumably caused by metabolic factors, such as decreased Na+/K+-ATPase activity, the altered polyol pathway, and tissue acidosis.
Action Potentials↗