Toshio Fukutake

Clinical features and prognosis of Miller Fisher syndrome

Article abstract— The authors reviewed the clinical features and outcome of Miller Fisher syndrome (MFS) for 50 consecutive patients with MFS including 28 patients who received no immunotherapy. Besides the characteristic clinical triad (ophthalmoplegia, ataxia, and areflexia), pupillary abnormalities, blepharoptosis, and facial palsy are frequent in MFS, whereas sensory loss is unusual despite the presence of profound ataxia. Patients with MFS usually had good recovery and no residual deficits.

Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease

BACKGROUND The genetic cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), which is characterized by ischemic, nonhypertensive, cerebral small-vessel disease with associated alopecia and spondylosis, is unclear. METHODS In five families with CARASIL, we carried out linkage analysis, fine mapping of the region implicated in the disease, and sequence analysis of a candidate gene. We also conducted functional analysis of wild-type and mutant gene products and measured the signaling by members of the transforming growth factor beta (TGF-beta) family and gene and protein expression in the small arteries in the cerebrum of two patients with CARASIL. RESULTS We found linkage of the disease to the 2.4-Mb region on chromosome 10q, which contains the HtrA serine protease 1 (HTRA1) gene. HTRA1 is a serine protease that represses signaling by TGF-beta family members. Sequence analysis revealed two nonsense mutations and two missense mutations in HTRA1. The missense mutations and one of the nonsense mutations resulted in protein products that had comparatively low levels of protease activity and did not repress signaling by the TGF-beta family. The other nonsense mutation resulted in the loss of HTRA1 protein by nonsense-mediated decay of messenger RNA. Immunohistochemical analysis of the cerebral small arteries in affected persons showed increased expression of the extra domain-A region of fibronectin and versican in the thickened tunica intima and of TGF-beta1 in the tunica media. CONCLUSIONS CARASIL is associated with mutations in the HTRA1 gene. Our findings indicate a link between repressed inhibition of signaling by the TGF-beta family and ischemic cerebral small-vessel disease, alopecia, and spondylosis.

Special sensory ataxia in Miller Fisher syndrome detected by postural body sway analysis

To investigate whether ataxia in Miller Fisher syndrome (MFS) is caused by loss of proprioception or cerebellar dysfunction, we studied the power spectrum peak of the body sway frequency in 10 MFS patients, and compared the results with those of patients with cerebellar or sensory ataxia. The cerebellar patients had a peak at 2.4 Hz, whereas sensory ataxia patients had a 1‐Hz peak. Nine of the MFS patients had a distinct 1‐Hz peak. Clinical sensory loss or abnormal sensory nerve potentials were present in only 3 patients, whereas soleus H‐reflexes were absent in all the MFS patients. MFS patients have dysfunction of the proprioceptive afferent system, and the special sensory ataxia may be caused by the selective involvement of muscle spindle afferents. Ann Neurol 1999;45:533–536

Familial Young-Adult-Onset Arteriosclerotic Leukoencephalopathy with Alopecia and Lumbago without Arterial Hypertension

Here we review a total of 17 patients, including 4 of our own, with young-adult-onset arteriosclerotic leukoencephalopathy, alopecia and lumbago without hypertension. All were Japanese and the illness seemed to be transmitted in an autosomal recessive fashion. The male to female ratio was 7.5:1. The age of onset usually ranged from 25 to 30 years. Acute lumbago, spondylosis deformans, diffuse baldness, and progressive motor and mental deterioration were common clinical features. Cerebral arteriosclerosis and white mater disease were demonstrated pathologically or radiologically. Although the pathogenesis has remained obscure, we think this is a new clinico-pathological entity distinct from the classic type of Binswangers disease.

Treatment and outcome of myasthenia gravis: retrospective multi-center analysis of 470 Japanese patients, 1999-2000.

To clarify the current status of treatments and outcomes of patients with myasthenia gravis (MG) in Japan, a total of 470 patients (164 men and 306 women; mean age 41 years) were recruited from 19 Japanese tertiary medical centers in 1999-2000. Thymectomy was performed in 319 (68%) of the patients. Patients who received thymectomy were younger (p = 0.01) and had more severe disabilities (p < 0.01) than patients without thymectomy. Irrespective of receiving thymectomy, most of the patients were administered corticosteroids (64%), other immunosuppressive agents (10%), or cholinesterase inhibitors (86%). Of 395 patients followed up for more than 12 months after treatment (mean 8.0 years), 30% (34% of thymectomized and 21% of non-thymectomized patients) were in remission (no symptoms with/without medication), 34% had only ocular symptoms, and the remaining 35% still had weakness of bulbar or limb muscles at the end of follow-up. The prognosis of MG in Japan was generally favorable, but despite the frequent use of thymectomy and immunosuppressive treatments, approximately one-third of patients still had generalized weakness. More effective or intensive treatments are required to improve the prognosis.

Fasciculation potentials in amyotrophic lateral sclerosis and the diagnostic yield of the Awaji algorithm

Introduction: The role of fasciculation potentials (FPs) in the diagnosis of amyotrophic lateral sclerosis (ALS) has been underrated. The Awaji algorithm has restored the value of FPs. Our aim was to test the diagnostic yield of the Awaji algorithm, with consideration of FPs. Methods: Subjects consisted of 139 consecutive ALS patients retrospectively enrolled over 5 years. At presentation we evaluated the diagnostic categories using the revised El Escorial Criteria (R‐EEC) and the Awaji algorithm. Results: The percentage of patients classified as confirmed ALS, clinically probable (laboratory‐supported), or higher was 43% using the R‐EEC and 37% using the Awaji algorithm. Thirteen patients with upper motor neuron signs only in one body region showed a decrease in their category using the Awaji algorithm. FPs were observed in 89% of ALS patients and were frequent in proximal muscles. Conclusion: The sensitivity of the Awaji algorithm is lower than that of the R‐EEC. Muscle Nerve, 2012

Plasmapheresis and Miller Fisher syndrome: analysis of 50 consecutive cases

Miller Fisher syndrome (MFS), characterised by the clinical triad of ataxia, ophthalmoplegia, and areflexia, is considered to be a variant form of Guillain-Barre syndrome (GBS). Large studies have shown that plasmapheresis1 and immunoglobulin treatment2 are beneficial for treating GBS. Because of the close relation between GBS and MFS, plasmapheresis may prove efficacious for treating MFS and has actually been tried in some cases. Moreover, because antibody to GQ1b is often present in serum from patients with MFS and is suggested to have a role in the pathophysiology of MFS, removing this antibody through plasmapheresis should have beneficial effects on patients with this syndrome. Although several reports have described possible plasmapheresis benefits in treating MFS,3,4 none has compared its clinical effects in patients treated and not treated with plasmapheresis. We conducted a retrospective analysis of 50 consecutive patients with MFS to clarify whether plasmapheresis enhanced the speed of recovery. Medical records of 53 patients with MFS, seen at Chiba University Hospital or its affiliated hospitals between 1979 and 1999, were reviewed. These patients were described in our previous investigation of the natural course of MFS.5 Criteria for inclusion in the study …

Auditory illusions caused by a small lesion in the right medial geniculate body

Although the medial geniculate body (MGB) is a well-known integration center for the central auditory pathways, auditory symptoms caused by MGB damage have not been described. We report the appearance of the auditory illusions of hyperacusis and palinacousis in a 49-year-old man without previous psychiatric or epileptic illness after a small hemorrhagic infarction located mainly in the right MGB.

Chronic Intractable Headache in a Patient With Marfan's Syndrome

A 30‐year‐old woman with Marfans syndrome had chronic intractable headaches and spontaneous intracranial hypotension. The pain was concentrated over the occipitonuchal region, had elements of both migraine and tension headache, and was often aggravated by postural change. Myelography showed multiple, large, lumbosacral arachnoid diverticula. Radioisotope cisternography revealed a halolike accumulation in the lumbosacral region and rapid uptake of isotope in the urinary bladder, indicating cerebrospinal fluid leakage. Epidural blood patching brought immediate relief from the positional headaches. We concluded that patients with Marfans syndrome and undifferentiated chronic headaches should be radiologically evaluated for spinal meningeal defects.

Roller coaster headache and subdural hematoma

Riding giant roller coasters may increase the risk of subdural hematomas. There have been three recent case reports on the topic.1–3 A 26-year-old man developed bilateral subdural hematomas after riding a double-loop, corkscrew-type roller coaster.1 A 64-year-old hypertensive man had headaches after his first roller-coaster ride and developed a left-sided chronic subdural hematoma after 11 more rides. These two cases had successful surgical evacuation.1–2 A fatal outcome was reported in a 73-year-old man being treated with warfarin.3 This patient developed a left-sided subdural hematoma and a parenchymal temporal hematoma 5 days after a roller-coaster ride. Despite surgery, he died 13 days later. We report the new case of a previously healthy woman who developed headaches and bilateral chronic subdural hematomas after a series of roller-coaster rides. A 24-year-old Japanese woman visited our hospital with a headache of 4 days duration. She was otherwise in good health and did not previously have headaches. …