We analyzed the results of the clock drawing test (CDT) in patients with Alzheimer’s disease (AD) by quantitative and qualitative methods to evaluate its significance for cognitive function screening. We administered the CDT and mini-mental state examination (MMSE) to a total of 156 AD patients, and CDT performance was scored quantitatively in accordance with the method by Freedman, while the CDT error types were qualitatively classified by Rouleau’s method. We divided AD patients into three groups by their MMSE total score (A: 23 ≤, B: 18~22, C: ≤ 17). The mean total scores of CDT and MMSE in AD were 11.5 ± 3.4 and 19.8 ± 4.7, respectively, and the total CDT scores showed significant positive correlation with the total MMSE scores (r = 0.450). Fewer than 80% of subjects drew the clock correctly for 8 out of 15 sub-items, and fewer were able to correctly draw clock hands than could correctly draw numbers, contour or a center. In analysis of CDT qualitative error types, the most common error types were spatial and/or planning deficit (SPD) (28.2%), and conceptual deficit (CD) (23.7%), which suggested visuospatial impairments and semantic impairments play essential roles in AD patients’ poor clock drawings. The frequency of CD and SPD error types significantly increased as severity of cognitive function worsened (p < 0.001, p < 0.05, respectively), and those of stimulus-bound response and perseveration had tendency to increase as severity of cognitive function. The present study suggests that CDT is a useful screening method not only for the impairment of cognitive function and the severity of cognitive dysfunction, but also for identification of specific cognitive function impairments in AD patients.

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We present a 46-year-old man with central pontine myelinolysis (CPM). He had been diagnosed with diabetes mellitus and chronic pancreatitis. He had drunk more than 1.2 l of Japanese sake daily for 20 years and more. He developed slight reduction of consciousness, dysarthria and truncal ataxia 7 days after he stopped drinking. The laboratory data on admission showed hyperosmolar hyperglycemic state, according to the following findings; glucose 1,058 mg/dl, serum osmolality 328 mOsm/l and serum sodium 119 mEq/l. According as administration of acetic Ringer’s solution and insulin injection, the laboratory data 14 hours after admission showed glucose 235 mg/dl, serum osmolality 290 mOsm/l and serum sodium 131 mEq/l. The initial diffusion weighted images (DWI) on MRI revealed a small high signal intensity spot in the pons. The second DWI after 14 days revealed a trident-shaped hyperintensity in the pons that was compatible with CPM. His symptoms showed no remarkable changes, but susceptibility weighted images of MRI after 4 months revealed low signal intensity area in the CPM lesion that indicated pontine hemorrhage. We speculate that marked fluctuation of serum osmotic pressure associated with the rapid change of the serum glucose had a significant role in the pathogenesis of the present case. Therefore, we recommend gradual correction of serum glucose and serum osmolality to maintain less than 12 mEq/l/day as correction of chronic hyponatremia in to prevent and ameliorate pathologic condition of CPM.

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A 66-year-old woman was admitted to our hospital with recurrent meningitis. She presented with 10 episodes of meningitis in 10 months. Examination of cerebrospinal fluid demonstrated pleocytosis, with neutrophils dominant at the early stage, and lymphocytes dominant at the late stage. Mollaret cells were found and the level of IL-6 was increased in cerebrospinal fluid. Several antibiotics and antiviral agents failed to prevent relapse. However, colchicine therapy successfully prevented the recurrence of meningitis. Genetic testing for familial Mediterranean fever (FMF) showed a mutation in the MEFV gene. It is difficult to diagnose the cause of Mollaret’s meningitis in some patients. FMF, neuro-Behçet’s disease, and neuro-Sweet disease should be included in the differential diagnosis of recurrent meningitis. In addition, colchicine therapy can prevent the relapse of meningitis in such cases.

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The patient was a 58-year-old man with 1-year history of cognitive decline, which was diagnosed as Alzheimer’s disease in another hospital. He was admitted to our hospital for extreme fatigue, weight loss, and dysphagia, subsequent to the left peripheral facial paresis. Brain magnetic resonance (MR) imaging showed bilateral diffuse white matter lesions and hippocampal atrophy. After admission, he presented with sudden high fever, recurrent exacerbations of consciousness, and increased C-reactive protein level with marked neutrophilia, with the result that he underwent mechanical ventilation. Routine cerebrospinal fluid findings at the exacerbation were normal i.e. 4.7 cells/mm³, 40 mg/dl of protein, but IL-6 concentration was mildly elevated to 22.2 pg/ml. After confirming the positivity of HLA (human leukocyte antigen) B54 and Cw1, we administered steroid to him and his physical activity and state of consciousness significantly improved. During the course of treatment, dermal lesion characterisitic of Sweet disease was absent. We diagnosed this case was possible neuroSweet disease proposed by Hisanaga in 2005.

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We present a case of callosal disconnection syndrome as a rare manifestation of acute disseminated encephalomyelitis (ADEM). A dextral 48-year-old Japanese woman received trivalent inactivated influenza vaccine in mid-November 2011. Twenty days later, she was found to be in a daze. Subsequently, she developed abnormal behavior and gait disturbance, and she was disoriented regarding time and place. Nystagmus and abnormal ocular movements were absent. Upper limb power was normal, whereas her lower limbs were mildly weak. Tendon reflexes were normally evoked without pathological reflexes. There was no sensory impairment. Serum CRP levels were slightly elevated; other routine laboratory tests, thyroid functions, and vitamin B₁ levels were within the normal range. Cerebrospinal fluid examination revealed that it was acellular with a protein level of 54 mg/dl and high myelin basic protein level. Fluid-attenuated inversion recovery MR images revealed a large hyperintense lesion in the corpus callosum, but the lower part of the splenium was spared. Flow voids were observed in the pericallosal arteries. She was diagnosed with post-vaccination ADEM and vigorously treated with an intravenous infusion of methylprednisolone (1 g/day for 6 days) and immunoglobulin (1.2 g/kg). Gait disturbance and disorientation rapidly improved; however, tactile anomia, ideomotor apraxia, ideational apraxia, and agraphia of the left hand were present one month after onset. She had no aphasia or alexia.Interestingly, the patient’s left unilateral agraphia was more prominent in kana than kanji (an article in Japanese text) for polysyllabic words, whereas she could write kana characters to dictation. Changes in the sequential order of kana characters within a word were observed. These findings were similar to those observed in pure agraphia associated with lesions in the posterior part of the left middle frontal gyrus. Thus, an interhemispheric mechanism is probably involved in the selection and arrangement of kana characters to form words.

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A 76-year-old woman was admitted to our hospital because of convulsions that developed after a 1-month history of progressive right-leg palsy. MRI showed thickening of the meninges with gadolinium enhancement in the left parietal lobe and it revealed pia-subarachnoid space pattern. A lumbar puncture was performed, and cerebrospinal fluid analysis revealed no abnormality. Her serum adenosine deaminase level was elevated (28.7 IU/l). The results of serum cultures were normal. To differentially diagnose collagen disease, infection, malignancy, and inflammation of uncommon causes, we conducted brain and meningeal biopsies on the 15th hospital day. Histopathological examination of the brain tissue showed mainly necrosis and inflammation. There was severe pachymeningeal thickening without necrosis. Although it was difficult to reach a definitive diagnosis, a tissue sample taken from under the leptomeninges tested positive for mycobacterium on Ziehl-Neelsen staining. The results of polymerase chain reaction for mycobacterium were negative in the meningeal tissue. The patient received anti-tuberculous drugs, anti-nontuberculous mycobacteriosis drugs, and corticosteroids to treat Mycobacterium tuberculosis and nontuberculous mycobacterium. After starting treatment, the findings on magnetic resonance imaging improved dramatically, and no convulsions occurred during hospitalization. She was discharged on the 153rd hospital day without any neurological deficit. Because previous studies have reported that isolated mycobacterium meningitis is a diagnostically challenging condition, brain and meningeal biopsies should be considered in patients with gadolinium enhancement in the meninges.

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An 80-year-old Japanese man developed sensory disturbance of his extremities. One week after the onset of sensory disturbance, he also developed bilateral facial nerve palsy, weakness of the extremities, vesicorectal disturbance, general fatigue, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). His symptoms worsened gradually. Despite the absence of apparent tick bite and characteristic skin lesions, we suspected Lyme neuroborreliosis (LNB) because of pleocytosis and elevated protein levels in the cerebrospinal fluid (CSF), in addition to the aforementioned symptoms. After combined administration of antibiotics and steroids, his symptoms improved rapidly. CSF showed highly elevated levels of the chemokine CXCL-13 and his serum was positive for IgM against Borrelia afzelii. Therefore, we diagnosed him as having LNB. He developed an exacerbation of SIADH and generalized fatigue during the course of LNB. His condition deteriorated despite further administration of antibiotics and steroids. Bone marrow aspiration revealed the presence of medium- to large-sized atypical lymphoma cells and lymphoma cells positive for CD8 but negative for CD45. Therefore, we diagnosed T-cell lymphoma. In recent years, an association between Borrelial infection and lymphoma development has been suspected. Borrelia afzelii infection may have been involved in the development of T-cell lymphoma in this case.

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A-68-year-old man experienced nuchal pain and bilateral shoulder weakness that occurred suddenly after he performed a golf swing. He was conscious. His cranial nerves were normal, but bilateral deltoid and biceps muscle strengths weakened. Magnetic resonance image (MRI) showed no brain stem infarctions or cervical epidural hematoma. We tentatively diagnosed him with concussion of the spinal cord because of mild recovery of his bilateral upper limb weakness after several hours; he was later discharged. The next day, he suddenly developed serious tetraplegia and was admitted to the emergency department. His breathing was controlled by a respirator as he had expectoration difficulty and respiratory muscle paralysis. A lesion in the cervical cord became apparent on MRI; the right vertebral artery was not detected on magnetic resonance angiography. Cervical MRI showed the intimal flap and a lack of flow void in the right vertebral artery. These findings revealed a right vertebral artery dissection. Cervical cord infarction due to unilateral vertebral artery dissection is rarer than posterior cerebral infarction due to the same pathogenesis; however, some such cases have been reported. We consider the present case to be caused by cervical cord infarction associated with unilateral vertebral artery dissection resulting from golf swing.

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A 73-year-old man developed double vision and a progressive loss of visual acuity of the left eye over one week. Examination showed disturbances of the left II, III, IV, and VI cranial nerves, that is, an orbital apex syndrome. A brain MRI showed abnormal T₂-high signals in the right maxillary sinus and the left mastoid cells without abnormalities in the left orbital apex and the surroundings. Laboratory examination showed an elevated erythrocyte sedimentation rate and a positive perinuclear anti-neutrophil cytoplasmic antibody (MPO-ANCA). After two courses of methyl-prednisolone pulse treatment, his external ophthalmoplegia fully recovered and he regained his left eye’s sight. MPO-ANCA was negative and MRI abnormalities were disappeared after treatment. Two years later, the patient developed upper respiratory symptoms associated with an elevation of MPO-ANCA titer, and rapidly progressive renal failure. Renal biopsy specimen showed fibrinoid necrosis with periarteriolar neutrophil infiltration, which suggested that the patient suffered from ANCA-associated vasculitis probably of Wegener’s granulomatosis or microscopic polyarteritis. ANCA-associated vasculitis may present with a focal neurological syndrome such as the orbital apex syndrome without a lesion detectable with MRI.

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An 82-year-old man had a transient ischemic attack (TIA) with symptoms of consciousness disturbance and right hemiparesis while resting in a sitting position after breakfast. His symptoms improved around 1 h after onset when he lied in a supine position and received intravenous hydration. Duplex carotid ultrasonography revealed severe stenosis of the left common carotid artery. A decrease in the brain perfusion reserve was confirmed by acetazolamide-stress brain perfusion scintigraphy. Moreover, ambulatory blood pressure monitoring revealed a reduction in systolic blood pressure below 90 mmHg after each meal, indicating postprandial hypotension (PPH). The PPH was improved by oral administration of α-glucosidase inhibitor without any subsequent recurrences of TIA. The patient was diagnosed with TIA of hemodynamic origin that was induced by PPH and exhibited severe carotid stenosis. PPH is common in elderly people, and it should be recognized as a significant trigger for ischemic cerebrovascular disease.

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[in Japanese]

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[in Japanese]

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