Takahiro Mezaki

Comparison of Therapeutic Efficacies of Type A and F Botulinum Toxins for Blepharospasm A double-blind, controlled study

Article abstract-Type F botulinum toxin can be used for treating patients with dystonia who become refractory to type A toxin injection due to antibody development. We compared the therapeutic efficacy of type F botulinum toxin to that of type A toxin in a self-controlled, double-blind clinical trial. In nine patients with blepharospasm, we injected type A toxin on one side and the same units of type F toxin on the other side. Although the onset of clinical effect, maximal benefit, and adverse reactions were similar between type A and F toxins, the duration of the clinical effect was significantly shorter on the side injected with type F toxin. Although type F toxin proved its promise as an alternative to type A toxin, its usefulness is limited by the shorter duration of action. NEUROLOGY 1995;45: 506-508

Low CSF hypocretin-1/orexin-A associated with hypersomnia secondary to hypothalamic lesion in a case of multiple sclerosis

Sirs: Hypocretins/orexins are hypothalamic neuropeptides that are related to sleep-wake regulation [1, 10]. It has been reported that cerebrospinal fluid (CSF) hypocretin1/orexin-A level is dramatically decreased in narcolepsy-cataplexy [4, 8, 9, 11]. Narcolepsy is also known to occur secondary to hypothalamic lesions caused by tumors, stroke, multiple sclerosis (MS) or acute disseminated encephalomyelitis, and the CSF hypocretin-1 level is decreased in some of them [5–7, 12]. However, it remains unclear whether CSF hypocretin level correlates with the severity of hypersomnia and the REM pathology. We reported the MRI finding of bilateral hypothalamic lesions in a case of MS presenting with hypersomnia [3]. We further examined details of sleep investigations and correlated them with CSF hypocretin-1 level and the MRI findings. A 22-year-old woman was admitted to our hospital one week after the acute onset of hypersomnia. She had developed diplopia as an initial symptom of MS one year before the onset of hypersomnia. She also complained of numbness of the lower extremities and polyuria. She did not experience any narcolepsy-related symptoms such as cataplexy, sleep paralysis and hypnagogic hallucination. MRI revealed bilateral FLAIR hyperintensity in the hypothalamus [3]. CSF showed increased myelin basic protein (242 pg/mL; normal < 100 pg/mL). CSF hypocretin-1 level was measured using radioimmunoassay kit (Phenix Pharmaceuticals, USA). HLA was positive for DR-4 and DR-6 but negative for DR-2. Sleep investigations including polysomnography (PSG) followed by multiple sleep latency test (MSLT) were performed 11days after the onset of hypersomnia. Methylprednisolone (1000 mg/day for 3 days) was started on the following day which was followed by oral prednisolone therapy, and her clinical symptom resolved within two weeks after methylprednisolone therapy was started. CSF hypocretin-1 level was undetectable (< 40 pg/mL; normal 200–350 pg/mL) on the first evaluation (Table 1). PSG showed sleep onset REM period (SOREMP), and confirmed the absence of any other sleep disorders. MSLT showed a mean sleep latency of 2.8 minutes and five SOREMPs out of five sessions. On the second evaluation two months later, the patient had no complaint of hypersomnia. Hypothalamic lesions were diminished. MSLT showed a mean sleep latency of 17.4 minutes and SOREMP appeared only once. CSF hypocretin-1 level was 167 pg/mL. On the third evaluation four months after the first one, MSLT showed a mean sleep latency of 14.8 minutes and no SOREMP. CSF hypocretin level was normal (211 pg/mL). This patient showed acute onset of hypersomnia but did not show cataplexy or any other narcolepsyrelated symptoms. Our case does not fulfill the diagnostic criteria of narcolepsy because the diagnosis of narcolepsy requires either cataplexy or other narcolepsy-related LETTER TO THE EDITORS

DYT1 mutation in Japanese patients with primary torsion dystonia.

A GAG deletion at position 946 in the DYT1 gene has been identified as one of the gene mutations responsible for autosomal dominant primary torsion dystonia. We examined 178 Japanese patients with various forms of dystonia, and found the mutation in six patients (3.4%) from three families. Five of them had early clinical onset (before age 12) with initial involvement of a limb. To our knowledge, this is the first report of the frequency and the clinical features of DYT1 mutation in oriental patients, and the clinical presentation of the mutation in these patients was similar to that of Jewish or non-Jewish Caucasian patients.

Hypersomnia in MS

Focal lesions can cause narcolepsy.1,2⇓ A 22-year-old woman with MS developed acute hypersomnia. Her first episode of MS occurred 9 months previously, when …

Heidenhain Variant of Creutzfeldtjakob Disease: Diffusion‐Weighted MRI and PET Characteristics

Creutzfeldt‐Jakob disease (CJD) is characterized by rapidly progressive dementia with a variety of neurological disorders and a fatal outcome. The authors present a case with visual disturbance as a leading symptom and rapid deterioration in global cognitive functions. The cerebrospinal fluid was positive for 14‐3‐3 protein, and diffusion‐weighted magnetic resonance imaging (MRI) showed marked hyperintensity in the parieto‐occipital cortices, where hypometabolism was clearly detected on positron emission tomography (PET). Pattern‐reversal visual evoked potentials showed prolonged P100 latencies and increased N75/P100 amplitudes. All these findings supported a diagnosis of the Heidenhain variant of CJD, whereas a long clinical course, a lack of myoclonus, and an absence of periodic synchronous discharges on electroencephalography were atypical. Diffusion‐weighted MRI and PET in combination with visual evoked potential recording and 14‐3‐3 protein detection may be useful for the early diagnosis of CJD.

Combined use of type A and F botulinum toxins for blepharospasm: A double-blind controlled trial

Type A botulinum toxin has widened its clinical range of applications, but the risk of developing antibodies limits the repeated use of high‐dose injection. To minimize the risk, mixing different types of toxin might reduce the antigenic presentation of a specific toxin and associated proteins. At the same time, inhibition of the neuromuscular release process at the multiple sites might potentiate the clinical response or the duration of action. We compared the effectiveness of a mixture of type A and type F botulinum toxins with that of type A or type F toxin alone for treating patients with blepharospasm in a double‐blind study. Fifty‐four patients had 10 units of toxin injection, a mixture of type A and F toxins (including 5 units of each) on one side and either type A or F toxin on the other side of the orbicularis oculi muscle. Clinical evaluation at 4 and 10 weeks after the injection revealed that the peak clinical effect at 4 weeks was similar among the three preparations. The duration of action of the mixture was intermediate between type A and type F alone, as assessed at 10 weeks, when there was a tendency of conserving the beneficial effect on one eye at the expense of that on the other. Although there was no apparent potentiation of the clinical efficacy, the combination of these different types of toxin might be used for decreasing the risk of antibody development.

Long-term effect of bone marrow transplantation in adult-onset adrenoleukodystrophy

We report a long‐term outcome of motor function in a patient with adult‐onset adrenoleukodystrophy after bone marrow transplantation (BMT). Clinically motor function gradually improved and became almost normal in 2 years after BMT. Serial transcranial magnetic stimulation showed gradual improvement of central motor conduction until 1 year after BMT, and then it became stable. Central motor conduction time and motor threshold were useful for monitoring the central motor function in this patient.

Dynamic change of proximal conduction in demyelinating neuropathies : a cervical magnetic stimulation combined with maximum voluntary contraction

OBJECTIVE To evaluate conduction abnormalities in the nerves innervating the proximal muscles in demyelinating neuropathies (DN) using cervical magnetic stimulation. METHODS We applied cervical root magnetic stimulation in the biceps brachii muscles and examined its activity-dependent conduction changes produced by maximal voluntary contraction (MVC) in 12 DN patients (seven chronic inflammatory demyelinating polyradiculoneuropathy and five multifocal motor neuropathy), six motor neuron disease (MND) patients, and 12 healthy volunteers. RESULTS Defining the upper normal limit of motor threshold (31%) and latency (6.7 ms) of the compound muscle action potential (CMAP) as mean+2SD, most DN patients revealed an abnormality in motor threshold (10/12) and latency (11/12) in contrast to MND patients (motor threshold (1/6) and latency (0/6)). These parameters contribute to the differentiation of DN from MND (P<0.01). Furthermore, the MVC maneuver transiently decreased the CMAP amplitude ratio (after MVC/before MVC x 100) in DN (83+/-18 %) compared with MND (P<0.01). Two of three DN patients who showed normal motor threshold or latency as in MND were successfully differentiated from MND by the MVC maneuver. CONCLUSIONS In DN patients, conduction abnormality in the nerves innervating the proximal muscles was revealed by cervical magnetic stimulation combined with the MVC maneuver. SIGNIFICANCE Our results suggested that conduction abnormalities in the proximal nerves innervating the proximal muscles could be evaluated by this method.

Treatment of spasticity with muscle afferent block

In 1924, Walshe1 first reported that intramuscular injection of diluted procaine reduced muscle rigidity in a patient with postencephalitic parkinsonism. Its mechanism of action was attributed to blockade of muscle afferents because the muscle motor response elicited by electric stimulation was unchanged. Since then, this method of treating muscle hyperactivity has been ignored because of its transient action. Recently we revived this muscle afferent block (MAB) by intramuscularly injecting 0.5% lidocaine together with 100% ethanol in a 10:1 volume ratio.2,3 The mixture is expected to work as a short-latency, long-duration anesthetic because ethanol in a 5 to 10% concentration is a long-acting sodium channel blocker.4 In addition to writer’s cramp2 and oromandibular dystonia,3 it is used for treating cervical dystonia.5 In MAB, the solution is not directly injected to the nerve or the motor point but is diffused into the whole muscle. It is technically easier and carries less risk of unexpected palsy or sensory deficits than the conventional nerve block with ethanol or phenol. Because the diluted anesthetic preferentially affects small-diameter fibers, such as …

Improvement of central motor conduction after bone marrow transplantation in adrenoleukodystrophy

The case is described of a 20 year old man with adrenoleukodystrophy who showed right spastic hemiparesis and gait disturbance. Brain magnetic resonance imaging disclosed predominant involvement of the left corticospinal pathway. The clinical symptoms improved after bone marrow transplantation. Transcranial magnetic stimulation disclosed significant improvement in various parameters of central motor conduction.