Kazutaka Jin

A case of NMO seropositive for aquaporin-4 antibody more than 10 years before onset

Neuromyelitis optica (NMO) is characterized by severe optic neuritis and longitudinally extended transverse myelitis (LETM). The clinical and laboratory features of NMO are different from multiple sclerosis (MS).1 An autoantibody to aquaporin-4 (AQP4) has been detected exclusively in the NMO sera.1 Moreover, we demonstrated an extensive loss of AQP4 and glial fibrillary acidic protein immunoreactivities in the perivascular regions with complement and immunoglobulin deposition in NMO that suggests astrocytic impairment. However, when AQP4 antibody is produced in patients with NMO is unknown, and thus it remains unresolved whether there are long-term asymptomatic AQP4 antibody–positive carriers, whether AQP4 antibody alone can be pathogenic, and whether AQP4 antibody is produced secondarily as a result of tissue destruction in attacks of NMO. We herein report a case of NMO in which AQP4 antibody was detected years before the NMO onset. ### Case report. A 34-year-old healthy woman without previous history of inflammatory or neurologic diseases noticed temporary skin eruptions on her chest and shoulders in June 2007. A dermatologist made the diagnosis of eczema. Three weeks later, when the skin eruptions subsided, she noted progressive paresthesia in the chest and toes. Within a few days, she could not walk well due to right leg weakness, and then she was hospitalized. Neurologic examination on …

Clinical features of Creutzfeldt-Jakob disease with V180I mutation

The authors describe the clinical features of Creutzfeldt-Jakob disease (CJD) with the causative point mutation at codon 180. The symptoms never started with visual or cerebellar involvement. The patients showed slower progression of the disease compared with sporadic CJD. They never showed periodic sharp and wave complexes in EEG. MRI demonstrated remarkable high-intensity areas with swelling in the cerebral cortex except for the medial occipital and cerebellar cortices. These characteristic MRI findings are an important clue for an accurate premortem diagnosis.

Transcranial magnetic stimulation alleviates truncal ataxia in spinocerebellar degeneration

Spinocerebellar degeneration is an inherited or acquired neurodegenerative disorder characterised by steadily progressive cerebellar ataxia, dysarthria, and gait disturbance. These symptoms restrict daily activities. However, no satisfactory therapy has been established. Transcranial magnetic stimulation (TMS), originally introduced to the medical field to evaluate the function of the CNS, is recently becoming a therapeutic tool for neuropsychiatric disorders, such as major depression1 and Parkinsons disease.2 We also reported the efficacy of TMS for inherited spinocerebellar degeneration.3 We now report here a placebo controlled trial of TMS over the cerebellum for patients with spinocerebellar degeneration. Seventy four patients with spinocerebellar degeneration gave written informed consent to participate in this study, which was approved by the ethics committee of Tohoku University. No patient had a history of seizures or any abnormalities established by EEG. They also had no orthopaedic problems. Thirty nine patients, aged from 27 to 76 years (19 men and 20 women), were assigned to active stimulation, and the other 35 patients, aged from 38 to 76 years (25 men and 11 women), were assigned to sham stimulation. They were divided based on the date when they were admitted to our hospitals. The age, disease duration (unpaired t test), disease type (χ2 test), and disease severity (unpaired t test) were matched between the two groups. Disease types were divided into two groups, cerebellar type (sporadic and hereditary cortical cerebellar atrophy including spinocerebellar atrophy (SCA) 6) and olivopontocerebellar atrophy (OPCA) type (sporadic OPCA, SCA1, SCA3, etc). Transcranial magnetic stimulation over the cerebellum was administered at almost the same time in the evening once a …

Familial leptomeningeal amyloidosis with a transthyretin variant Asp18Gly representing repeated subarachnoid haemorrhages with superficial siderosis

Objectives: To report the clinical features of two Japanese brothers with familial leptomeningeal amyloidosis, showing a causative gene abnormality of a transthyretin (TTR) variant Asp18Gly, previously reported only in a Hungarian family. Methods: The authors reported on a 42 year old man (patient 1) and his 45 year old brother (patient 2), both suffering from subarachnoid haemorrhage (SAH) without and with hydrocephalus, respectively. DNA sequences of the TTR gene were determined in both patients and the patients’ clinical features described. A surgical biopsy of the leptomeninges was performed on patient 1. Results: DNA sequence analyses demonstrated the glycine-for-aspartate substitution at position 18 of the TTR variant. Both patients revealed pyramidal tract signs and cerebellar ataxia. Audiometric studies showed bilateral, mild sensorineural hearing loss in the patients whose cerebrospinal fluid (CSF) protein levels increased. T1 weighted MRI after contrast administration showed diffuse leptomeningeal enhancement along the Sylvian fissures and over the surface of the brainstem, cerebellum, and spinal cord. Gradient echo T2* weighted MRI showed superficial siderosis mainly in the cerebellum. A biopsy of the leptomeninges was obtained from the spinal cord of patient 1. While performing the biopsy, the authors observed the varicose, elongating, and fragile veins on the dorsal surface of the spinal cord. Immunohistochemical study revealed marked deposits of TTR derived amyloid on his leptomeninges. Conclusions: This is the second report of familial leptomeningeal amyloidosis with an Asp18Gly TTR gene mutation, clinically causing only CNS symptoms. Repeated SAH from fragile veins on the dorsal surface of the spinal cord seemed to induce superficial siderosis of the CNS. So far, there have been two reliable hallmarks leading to the diagnosis of leptomeningeal amyloidosis: diffuse leptomeningeal enhancement on contrast MRI and greatly increased CSF protein content. This study has contributed a third hallmark: the presence of superficial siderosis is useful in diagnosing leptomeningeal amyloidosis.

CSF protein biomarkers for proximal axonal damage improve prognostic accuracy in the acute phase of Guillain‐Barré syndrome

Early predictors of prognosis in Guillain‐Barré syndrome (GBS) are needed to identify patients who are likely to make a poor recovery and to guide therapeutic decision‐making in the acute phase. Here we investigate whether axonal protein biomarkers released into the cerebrospinal fluid (CSF) following proximal axonal damage improve the early prognostic accuracy in GBS. A prospective multicenter study including 132 patients (38 GBS, 38 neurological controls, 42 headaches, 14 chronic inflammatory demyelinating neuropathy). CSF levels of axonal [neurofilament (NfH) and tau] and glial (S100B and glial fibrillary acidic protein) protein biomarkers were measured on admission. Nerve conduction studies were performed at the time of lumbar puncture and patients were classified according to neurophysiological criteria. Outcome was assessed on the Hughes functional score (F‐score). Poor outcome was defined as the inability to walk independently (F‐score ≥3). High NfH levels (>0.73 ng/ml) predicted poor outcome (P = 0.01) with an odds ratio of 7.3 and correlated with the outcome F‐score (R = 0.51, P < 0.01), as did hTau levels (R = 0.47, P < 0.01). Patients with poor outcome had significantly higher CSF NfH (median 1.78 ng/ml) when compared to those with good outcome (0.03 ng/ml) or all of the control groups (neurological controls 0.18 ng/ml, headaches 0.06 ng/ml, chronic inflammatory demyelinating neuropathy 0.05 ng/ml). Except for age (P < 0.05) and need for ventilatory support (P < 0.05), none of the other features reliably predicted outcome. Improved prognostic accuracy in the acute phase of GBS seems possible using CSF NfH levels. Muscle Nerve 40: 42–49, 2009

Magnetic source imaging and ictal SPECT in MRI‐negative neocortical epilepsies: Additional value and comparison with intracranial EEG

Purpose:  To investigate the utility of magnetic source imaging (MSI) and ictal single photon emission computed tomography (SPECT), each compared with intracranial electroencephalography (EEG) (ICEEG), to localize the epileptogenic zone (EZ) and predict epilepsy surgery outcome in patients with nonlesional neocortical focal epilepsy.

Tracheostomy can fatally exacerbate sleep-disordered breathing in multiple system atrophy.

TRACHEOSTOMY CAN FATALLY EXACERBATE SLEEP-DISORDERED BREATHING IN MULTIPLE SYSTEM ATROPHY To the Editor: I read the article by Jin et al.1 with interest. I am concerned that the title is misleading and not supported by the authors’ data. The phenomenon of central sleep apnea (CSA) developing after tracheostomy in multiple system atrophy (MSA) has been noted before and is of uncertain prognostic significance.2,3 Jin et al. describe CSA in seven patients following tracheostomy for vocal cord paralysis. In three patients, polysomnography (PSG) was also performed before surgery. However, comparison of the studies showed that obstructive apneas had changed to central apneas in one patient with a lower apneahypopnea index while pre-existing central apneas had increased in frequency in the other two. As pre-tracheostomy PSG was not reported in the other four patients, it is impossible to know whether there was any change in apnea type or severity. The authors do not mention that any of the patients died during the course of the study. Table e-1 on www.neurology.org indicates that the three patients with both preand posttracheostomy studies survived a mean of 11.4 years from disease onset and 5.8 years after tracheostomy (range 4.3–8.0 years). As the mean life expectancy in MSA is 8 to 10 years from onset,4 there is no evidence that tracheostomy resulted in reduced life expectancy by “fatally” exacerbating sleep disordered breathing. CSA should be distinguished from central neurogenic hypoventilation in MSA. The latter condition can result in hypercapnic respiratory failure and may be a factor causing death even in patients who have undergone tracheostomy. However, the patients described by Jin et al. actually had lower Paco2 levels than before tracheostomy with no evidence for hypoventilation. The presence of laryngeal stridor is associated with reduced survival in MSA5 and there are many reports of sudden death occurring within days to weeks of identification of stridor. While the first line treatment for mild stridor in MSA is probably continuous positive airway pressure (CPAP) therapy, tracheostomy remains the recommended choice for patients with daytime stridor, immobile vocal cords on laryngoscopy, or stridor unresponsive to CPAP. The article by Jin et al. may lead neurologists to erroneously believe that tracheostomy is harmful in this population and should be avoided. On the contrary, it can save lives in selected patients.

Magnetic source imaging in non-lesional neocortical epilepsy: Additional value and comparison with ICEEG

OBJECTIVE To investigate the utility of magnetic source imaging (MSI) for localizing the epileptogenic zone (EZ) and predicting epilepsy surgery outcome in non-lesional neocortical focal epilepsy (NLNE) patients. METHODS Data from 18 consecutive patients with NLNE who underwent presurgical evaluation including intracranial electroencephalography (ICEEG) and MSI were studied. Follow-up after epilepsy surgery was ≥24 months. Intracranial electroencephalography and MSI results were classified using a sublobar classification. RESULTS Sublobar ICEEG focus was completely resected in 15 patients; seizure-free rate was 60%. Eight patients showed sublobar-concordant ICEEG/MSI results and complete resection of both regions; seizure-free rate was 87.5%. Seizure-free rate in cases not matching these criteria was only 30% (p=0.013). CONCLUSIONS Magnetoencephalography is a useful tool to localize the EZ and determine the site of surgical resection in NLNE patients. When sublobar concordance with ICEEG is observed, MSI increases the predictive value for a seizure-free epilepsy surgery outcome in these patients.

CSF TAU PROTEIN: A NEW PROGNOSTIC MARKER FOR GUILLAIN-BARRÉ SYNDROME

We measured the CSF tau protein levels in 26 patients with Guillain-Barré syndrome. The levels of the poor outcome group (Hughes grade at 6 months was between II and VI, n = 6) were higher than those of the good outcome group (0 or I, n = 20) (p < 0.0005). The higher levels of CSF tau may reflect axonal degeneration and could predict a poor clinical outcome in Guillain-Barré syndrome.

Complete remission of seizures after corpus callosotomy

OBJECT Corpus callosotomy is usually intended to alleviate-not to achieve total control of-epileptic seizures. A few patients experience complete seizure control after callosotomy, but the associated clinical factors are unknown. The object of this study was to investigate clinical factors associated with long-term seizure remission after total corpus callosotomy in patients with infantile or early childhood onset epilepsy. METHODS Thirteen consecutive patients with infantile or early childhood onset epilepsy underwent 1-stage total corpus callosotomy for alleviation of seizures. Their age at surgery ranged from 1 year and 5 months to 24 years (median 7 years). Eleven patients had West syndrome at the onset of disease, and the other 2 had Lennox-Gastaut syndrome. All patients suffered from spasms, axial tonic seizures, or atonic seizures. Six patients had proven etiology of epilepsy, including tuberous sclerosis, polymicrogyria, trauma, and Smith-Magenis syndrome. The association between postoperative seizure freedom and preoperative factors including age at surgery, no MRI abnormalities, proven etiology, and focal electroencephalographic epileptiform discharges was examined. RESULTS Postoperative seizure freedom was achieved in 4 of 13 patients for a minimum of 12 months. All 4 patients had no MRI abnormalities and no identified etiology. None of the 8 patients with MRI abnormality, 6 patients with known etiology of epilepsy, or 4 patients aged older than 10 years at surgery achieved seizure freedom. Two of the 7 patients with focal electroencephalographic abnormalities became seizure free. Absence of MRI abnormalities was significantly associated with postoperative seizure freedom (p < 0.01). CONCLUSIONS Complete seizure remission is achieved after total corpus callosotomy in a subgroup of patients with intractable epilepsy following West syndrome or Lennox-Gastaut syndrome. One-stage total corpus callosotomy at a young age may provide a higher rate of seizure freedom, especially for patients with no MRI abnormalities and no identified etiology of epilepsy.