Tsutomu Kamo

PCR-Based Method for Isolation and Detection of Chlamydia pneumoniae DNA in Cerebrospinal Fluids

ABSTRACT Since current studies indicate the possible involvement ofChlamydia pneumoniae in the pathogenesis of multiple sclerosis (MS), demonstration of C. pneumoniae in the cerebrospinal fluid (CSF) of patients with MS is highly desirable. However, there is controversy concerning the detection of C. pneumoniae in CSFs from MS patients due to the lack of a standard protocol for extraction and detection of C. pneumoniae DNA. In this regard, we attempted to establish a highly effective extraction protocol for C. pneumoniae DNA from CSFs utilizing a commercial kit and a PCR detection method. The extraction and PCR detection protocol established in this study succeeded in detecting as few as 20 C. pneumoniae organisms in 200 μl of mock CSF. The use of this protocol to detect C. pneumoniae DNA in CSFs revealed that 68% of CSF samples obtained from patients with MS were positive (11 out of 16 samples) for chlamydia DNA. Thus, the protocol established here is sensitive enough to detect chlamydia DNA from CSFs and can be used by other laboratories for evaluation of the presence of chlamydiae in CSFs because the protocol is based on the use of a commercial kit.

Internal ophthalmoplegia with anti-GQ1b IgG antibody.

Sirs: Bickerstaff ’s brainstem encephalitis (BBE) is characterized by acute ophthalmoplegia and cerebellar ataxia preceded by infection. While generally considered a variant of Guillain-Barré syndrome, Fisher syndrome (FS) is believed by some neurologists to involve the brainstem [1]. Owing to the apparent similarities in the clinical presentations of FS and BBE, opinions differ as to whether the two syndromes are distinct or related, and to whether the causative lesions occur in the peripheral or central nervous system. Patients with BBE do exhibit symptoms and signs of central nervous system involvement, such as somnolence, brisk reflexes, or abnormal plantar response. High titers of anti-GQ1b IgG antibodies are detected in patients with BBE as well as in those with FS and Guillain-Barré syndrome [3, 9]. While the fact that BBE and FS share a common autoantibody suggests that they are closely related conditions, the final diagnoses must be based on clinical signs. The antiGQ1b IgG antibody is closely associated with acute paresis of extraocular muscles. This GQ1b ganglioside is highly enriched in the paranodal regions of the extramedullary portion of the oculomotor, trochlear, and abducens nerves [3]. Here, we report a case of BBE in which the initial symptom was photophobia, the first such case to be reported. Our patient showed minimal limitation of ocular movement, but her serum contained the anti-GQ1b IgG antibody.We performed a pharmacological study of the pupils, and here discuss the lesion likely to be responsible. A 53-year-old woman experienced sneezing and nasal discharge, which improved over the course of two days. She reported right ocular pain and exhibited reddish eruptions on her arms caused by consumption of milk or eggs and a nettle rash resulting from cold stimulations like water on the skin. Two days after the resolution of sneezing and nasal discharge, she noted hyperesthesia on her face and throat when contacted by cold wind or water. On the following day, she developed photophobia, diplopia, headache, and vomiting (day 1). She was admitted on day 6. The patient demonstrated alertness and normal mental functions. Her pupils were isocoric, both 7.0 mm in diameter, with minimal impairment of the upward gaze. The other directions of ocular movement were not limited. Light and accommodation reflexes were absent. There was no weakness in the extremities. There was slightly increased tonus in the muscles of both legs as well as mild truncal ataxia, and the deep tendon reflexes were symmetrically increased.Neck stiffness was not present. There was no impairment of pinprick, touch, position sense, or vibratory sensation. Autonomic nervous function was normal, as were the results of routine hematological and blood chemical tests. The cerebrospinal fluid protein was 23 mg/dl (normal 15~45 mg/dl) with 4 mononuclear cells/ l (normal < 5/ l).Viral screening of blood and CSF (including screening for the herpes simplex virus and cytomegalovirus) was unremarkable. MRI of the brain and spinal cord showed no abnormalities. An electroencephalographic examination also failed to show abnormalities. Auditory brainstem responses, nerve conduction studies, and Fwave responses were all normal. The patient was treated with acyclovir and methylprednisolone. An enzyme-linked immunosorbent assay showed that the serum IgG obtained on day 6 reacted strongly with GQ1b (1:64000), but not with GM1, GM2, GD1a, GalNAc-GD1a, GD1b, GD2, or GT1b. The patient was prescribed 1000 mg of methylprednisolone on days 7, 8, 9, 21, 22, and 23. Her food allergies disappeared after the first steroid pulse. On day 45, the left pupil responded to light, contracting from 7.0 mm to 6.0 mm. Two months after the onset of neurological signs, the anti-GQ1b IgG antibody titer became 1:16000. Tendon reflexes remained increased, and mydriasis persisted, with the left pupil smaller and slightly oval in shape. A limited pupillary light reaction and near response were present bilaterally, more marked on the right side. Ocular gaze limitation diminished,and the diplopia gradually improved (Figure). Results of pharmacological tests involving the patient’s pupils two months after onset were as follows: pilocarpine 0.125 % caused pupillary constriction from 7.0 mm to 4.0 mm on the right and from 6.0 mm to 3.0 mm on the left; 1.25 % epinephrine caused slight dilation from 6.0 mm to 7.0 mm on the right, and from 5.0 mm to 7.0 mm on the left; while 5 % cocaine also caused dilation from 6.0 mm to 7.0 mm on the right, and from 5.0 mm to 6.0 mm on the left. Five months after the onset of symptoms, the ocular gaze limitations and diplopia had almost disappeared, but other neurological signs persisted. The anti-GQ1b IgG antibody titer became 1:8000. The main clinical feature of our patient was the presence of bilateral LETTER TO THE EDITORS

Natural course of combined limb and palatal tremor caused by cerebellar‐brain stem infarction

After infarction of the left superior cerebellar peduncle and dentate nucleus, a patient developed tremor of the left upper limb beginning on the twelfth day followed by palatal tremor appearing 10 months after infarction. Surface electromyogram revealed a difference in the frequency of the tremor in the upper limb and soft palate. When the palatal tremor appeared, brain magnetic resonance T2‐weighted images revealed high signal intensity of the contralateral, right inferior olivary nucleus. Subsequently, when the amplitude of palatal tremor became less severe, the high olivary signal intensity subsided whereas the hypertrophy of the nucleus remained. This patient provides useful information on the pathogenesis of skeletal and palatal tremor with brain stem or cerebellar lesions based on the differences in the onset and frequency of tremors and morphologic changes in the inferior olive.

A case of primary lateral sclerosis taking a prolonged clinical course with dementia and having an unusual dendritic ballooning

Motor neuron disease associated with dementia has provided unique opportunities for studying the pathomechanisms of both disorders. In most instances, the former is amyotrophic lateral sclerosis (ALS). In this paper, we report a case of primary lateral sclerosis (PLS) with dementia. An adult female developed slowly pro‐gressive spastic paraparesis and dementia over a period of 17 years and died at the age of 55. Autopsy disclosed neuronal loss of the motor cortex and prominent degeneration of the pyramidal tract. Cranial and spinal motor neurons were well preserved. Neither Bunina bodies nor ubiquitin‐positive inclusions were detected. The findings were compatible with PLS. Diffuse cerebral atrophy, and marked atrophy of the striatum and the thalamus was observed. Senile plaques and Alzheimers neurofibrillary tangles were absent, but an unusual clear ballooning of dendrites was observed in the molecular and Purkinje cell layers of the cerebellum, and the anterior horn of the spinal cord. Together with reports of two similar cases, it is suggested that this case should be categorized as a rare disease entity of PLS with dementia.

Pharmacokinetics of cefotaxime in elderly patients.

With increasing age, the kidney shows a decrease in function as well as morphological changes. The principal cause of these changes is nephrosclerosis, which is considered to be one result of the systemic arteriosclerosis which progresses with age. A rapid increase in the incidence of nephrosclerosis is seen after 60 years of age (Maeda et al. 1981). Accordingly, when an antibiotic is to be administered to elderly patients , it is necessary to consider the dosage and administration method even in patients with a normal serum creatinine concentration and creatinine clearance, but especially in patients with decreased renal function. In the present study cefotaxime was administered to elderly patients, and the effects of ageassociated decreased renal function on the serum half-life and urinary excretion rate were studied. In addition, accumulation of cefotaxime was studied by administering it for 7 or more consecutive days.

Effects of indeloxazine hydrochloride on activities of daily living in cerebrovascular disease: Evaluation by accelerometer

Abstract The effect of indeloxazine hydrochloride (60 mg/day) on activities of daily living was evaluated in 12 patients with cerebrovascular disease. An accelerometer was used to monitor body acceleration in three planes over a 24-hour period before and after drug administration. A comparative group of five patients received ticlopidine hydrochloride (300 mg/day) under the same conditions. After 8 weeks of drug administration, the total level of activity over the 24-hour monitoring period was significantly higher in the indeloxazine group than in the ticlopidine group. Indeloxazine was found to improve nighttime activity as well.

Elderly onset Parkinson's disease complicated by dropped head syndrome that responded favorably to therapy*

An 86‐year‐old man presented with a 7‐year history of gait disturbance. He was admitted to hospital in April 2000, as he was experiencing difficulty eating due to progression of dropped head syndrome. Both standing and sitting, marked dropped head and kyphosis were observed. When supine, the patient was able to stretch his neck, and he could stand and walk with the aid of a walker. Rigidity and resting tremor were present predominantly in the lower limbs. Parkinsons disease was diagnosed, and L‐dopa and cabergoline were administered. Parkinsonism and dropped head syndrome improved in response to treatment. Cases involving Parkinsons disease are reportedly improved by L‐dopa, but exacerbated by dopamine agonists. Dropped head syndrome is thought to attributable to imbalances in the tonus of the anterior and posterior neck muscles. Dropped head in the present case may have been a complication of Parkinsons disease, since improvements occurred in response to L‐dopa.

Usefulness of switching to cabergoline from other dopamine agonists in patients with advanced Parkinson’s disease

Summary. Problems associated with long-term treatment of advanced Parkinson’s disease (PD) include motor complications and psychotic and autonomic symptoms. We switched patients from bromocriptine (BR) or pergolide (PER) to cabergoline (CB) therapy and investigated CB’s usefulness in alleviating such problems. Subjects were 30 patients (mean age 68.2 years; 13 receiving BR, 17 PER) with PD complicated by effects of long-term treatment but in whom their dose of dopamine (DA) agonist was contraindicated due to adverse reactions. Patients were switched to CB over a 2–4-week period. Hoehn-Yahr and Unified Parkinson Disease Rating Scale (UPDRS) I–IV “on” and “off” scores improved in both the BR and PER groups. CB was not discontinued due to adverse reactions in any patient. In conclusion, switching to CB is useful in patients in whom it is problematic to increase their dose of DA agonist due to motor complications or psychotic symptoms of advanced PD.

Vertical gaze palsy induced by midbrain lesions and its structural imaging

We experienced four cases of vertical gaze palsy induced by midbrain lesions. Lesions commonly covered the rostral midbrain, including the rostral interstitial nucleus, dorsomedial to the red nucleus. Two of the four cases resulted from vascular insult, in which a single, unpaired perforator is supposed to innervate the rostral midbrain and medial thalamus bilaterally. One case showed vertical gaze palsy accompanied by bilateral ptosis. The findings agree with recent experimental evidence that a neural substrate in eyelid control lies in the supraoculomotor area immediately dorsal to the oculomotor nucleus. The remaining two cases, a brain hemorrhage and an inflammatory tumor, showed unilateral lesions of the rostral midbrain. In these cases, vertical gazes were not abolished, but were limited in an incomplete way. This may be explained by partial damages of the descending fibers, some of which decussate through the posterior commissure before it reaches the oculomotor nucleus. Thus, clinical signs and symptoms were clarified based on anatomical and physiological points of view.

Serum somatostatin in early-stage Parkinson’s disease

Shiraishi M, Kobayashi T, Watanabe H, Kamo T, Hasegawa Y. Serum somatostatin in early‐stage Parkinson’s disease.
Acta Neurol Scand: 2010: 121: 225–229.
© 2009 The Authors Journal compilation