Therapeutic efficacy of heparin and direct factor Xa inhibitors in cancer-associated cryptogenic ischemic stroke with venous thromboembolism.

BACKGROUND: Anticoagulation therapy, especially using heparin or recently developed oral direct factor Xa inhibitors (DiXals), is recommended as first-line treatment for cancer-related venous thromboembolism (VTE). However, the preventive efficacy of these anticoagulants for cancer-associated ischemic stroke is still unknown. We retrospectively investigated the efficacy of subcutaneous unfractionated heparin (UFH) and DiXals for preventing the recurrence of cancer-associated cryptogenic ischemic stroke with VTE. METHODS: We retrospectively studied consecutive patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE who received subcutaneous UFH or oral DiXaIs at 9 hospitals. RESULT: Fifty-three patients (24 treated with UFH and 29 treated with DiXaIs) were enrolled. Of these, 47 demonstrated systemic metastasis (cancer stage IV). During 30-day follow-up after initiation of anticoagulation therapy, recurrent ischemic stroke was observed in only 1 patient (4%) in the UFH group and in 9 patients (31%) in the DiXal group. The incidence of major bleeding complications was similar between the 2 groups (4% and 10%, respectively). The cumulative risk of ischemic stroke recurrence within 30 days was lower with UFH than with DiXals (competing risk analysis, p = 0.008). In the DiXal group, patients who experienced recurrence showed significantly higher D-dimer levels than those without recurrence. CONCLUSION: In patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE, UFH demonstrated a lower rate of recurrent ischemic stroke than DiXaIs, and there were no differences in bleeding risk between the 2 treatments. D-dimer levels at stroke onset increased the risk of recurrence in the DiXal group but not in the UFH group.

Anti-TIF1-γ antibody and cancer-associated myositis: A clinicohistopathologic study.

OBJECTIVE: We aimed to analyze the clinical and histopathologic features of cancer-associated myositis (CAM) in relation to anti-transcriptional intermediary factor 1 γ antibody (anti-TIF1-γ-Ab), a marker of cancer association. METHODS: We retrospectively studied 349 patients with idiopathic inflammatory myopathies (IIMs), including 284 patients with pretreatment biopsy samples available. For the classification of IIMs, the European Neuromuscular Center criteria were applied. Patients with CAM with (anti-TIF1-γ-Ab[+] CAM) and without anti-TIF1-γ-Ab (anti-TIF1-γ-Ab[-] CAM) were compared with patients with IIM without cancers within and beyond 3 years of myositis diagnosis. RESULTS: Cancer was detected in 75 patients, of whom 36 (48%) were positive for anti-TIF1-γ-Ab. In anti-TIF1-γ-Ab(+) patients with CAM, cancers were detected within 1 year of myositis diagnosis in 35 (97%) and before 1 year of myositis diagnosis in 1. All the anti-TIF1-γ-Ab(+) patients with CAM satisfied the dermatomyositis (DM) criteria, including 2 possible DM sine dermatitis cases, and were characterized histologically by the presence of perifascicular atrophy, vacuolated fibers (VFs), and dense C5b-9 deposits on capillaries (dC5b-9). In contrast, 39 anti-TIF1-γ-Ab(-) patients with CAM were classified into various subgroups, and characterized by a higher frequency of necrotizing autoimmune myopathy (NAM). Notably, all 7 patients with CAM classified into the NAM subgroup were anti-TIF1-γ-Ab(-) and exhibited no dC5b-9 or VFs. CONCLUSIONS: CAM includes clinicohistopathologically heterogeneous disease entities. Among CAM entities, anti-TIF1-γ-Ab(+) CAM has characteristically shown a close temporal association with cancer detection and the histopathologic findings of dC5b-9 and VFs, and CAM with NAM is a subset of anti-TIF1-γ-Ab(-) CAM.

Interleukin 10 Level in the Cerebrospinal Fluid as a Possible Biomarker for Lymphomatosis Cerebri.

A 71-year-old immunocompetent man developed cognitive decline and gait disturbance. Brain magnetic resonance imaging (MRI) revealed bilateral diffuse leukoencephalopathy without a mass lesion. An analysis of the cerebrospinal fluid (CSF) showed elevated levels of interleukin (IL)-10. The condition of the patient progressively deteriorated, and intravenous high-dose steroids proved ineffective. Detection of non-destructive, diffusely infiltrating, large B-cell lymphoma in biopsy and autopsy specimens led to a diagnosis of lymphomatosis cerebri (LC). On serial MRI, the basal ganglia and white matter lesions increased in parallel with the levels of IL-10. These findings suggest that the IL-10 level in the CSF may represent a potentially useful biomarker for the early diagnosis and monitoring of the disease progression in LC.

The spectrum of clinicopathological features in pure autonomic neuropathy.

We assessed the clinicopathological features of nine patients with pure autonomic neuropathy, that is, neuropathy without sensory or motor deficits. The duration from symptom onset to diagnosis ranged from 1 month to 13 years. Of eight patients in whom serum antiganglionic acetylcholine receptor antibody was determined, four were positive. All patients who tested positive for this antibody manifested widespread autonomic dysfunction, with the exception of one patient who only experienced orthostatic hypotension. However, patients who were negative for the antiganglionic acetylcholine receptor antibody presented with partial autonomic failure. One of these patients had diffuse parasympathetic failure and generalized hypohidrosis but no orthostatic hypotension, which is clinically compatible with postganglionic cholinergic dysautonomia. Electron microscopic examination revealed a variable degree of reduction in unmyelinated fibers. Compared with normal controls, the patients had a significantly increased density of collagen pockets (p < 0.05). Additionally, the percentage of Schwann cell subunits with axons (out of the total number of Schwann cell subunits associated with unmyelinated fibers) was significantly decreased (p < 0.01). The density of unmyelinated fibers tended to decrease with increasing time between the onset of autonomic symptoms and biopsy (p < 0.05). In conclusion, the clinical and pathological features of pure autonomic neuropathy vary in terms of progression, autonomic involvement, presence of the antiganglionic acetylcholine receptor antibody, and loss of unmyelinated fibers.

Cilostazol versus aspirin therapy in patients with chronic dizziness after ischemic stroke.

BACKGROUND: Chronic dizziness is frequently reported by patients in the chronic stage after ischemic stroke. The aim of this study was to determine the efficacy of cilostazol versus that of aspirin for the chronic dizziness that follows ischemic stroke. METHODS: We performed a prospective, randomized, open-label, blinded endpoint trial. One hundred six patients who suffered supratentorial ischemic stroke within the previous 1-6 months and subsequently complained of persistent dizziness without other obvious sequelae were enrolled. Patients were randomly given cilostazol (200mg/day) or aspirin (100mg/day) for 6 months. Rates of improvement in the dizziness were then evaluated. Changes in fixation suppression of the vestibulo-ocular reflex (an indicator of cerebral control over the brainstem reflex related to balance), regional cerebral blood flow (CBF) in the cerebrum, cerebellum, and brainstem; and the Zung Self-Rating Depression Scale (SDS) were also evaluated. RESULTS: Dizziness was significantly improved in the cilostazol group versus the aspirin group (P<0.0001) after the 6-month therapy. The capacity for fixation suppression of the vestibulo-ocular reflex was improved (P<0.0001), and regional CBF in the cerebrum (relative to that in the brainstem [P=0.003] and to that in the cerebello-brainstem [P=0.012]) was increased only in the cilostazol group. There was no statistical difference in the change in SDS scores between the two groups. CONCLUSION: Cilostazol improves the chronic dizziness that follows ischemic stroke and increases supratentorial CBF and cerebral function for adaptation of the brainstem reflex related to the sense of balance.

Dementia and capsular genu ischemia in patients with severe bacterial meningitis.

Infarction in the genu of the internal capsule causes dementia that is characterized by abulia, lethargy and memory loss without obvious motor palsy (capsular genu syndrome). We found infarction or decreased cerebral blood flow in the genu of the internal capsule in 6 of 13 patients with severe bacterial meningitis. Four of these six patients developed post-meningitis dementia, characterized by abulia, lethargy, and memory loss. Of 24 patients with viral meningitis, none developed capsular genu ischemia or post-meningitis dementia. In patients with severe bacterial meningitis, capsular genu ischemia may play some role in the development of post-meningitis dementia. In patients with viral meningitis, absence of such ischemia may explain, at least in a part, the rarity of post-meningitis dementia.

Jugular phlebectasia: a manometric study in an unanesthetized patient.

Jugular phlebectasia, a dilatation of the jugular veins, is a relatively rare benign condition. Although the precise etiology is unknown, an increase in intrathoracic pressure that is transmitted to the jugular vein is believed to cause the venous ectasia. However, in this case of a 70-year-old woman with right internal jugular phlebectasia, the increase in intrathoracic pressure was not transmitted to the dilated vein, although it was transmitted to the other surrounding veins. Selectively high baseline pressure in the dilated vein could have caused the venous ectasia in this case.

Spike-wave stupor in a patient with metabolic disorder.

We report a 79-year-old woman with a decreased level of consciousness. Investigation revealed an elevated serum ammonia and a portal-systemic shunt on angiography. Thus, her symptoms were thought to be due to metabolic encephalopathy. Her electroencephalogram (EEG) showed bilaterally synchronous runs of three-phase waves consistent with the triphasic waves typically seen in metabolic encephalopathy. However, after intravenous administration of diazepam, the EEG abnormalities improved; indicating that her decreased consciousness was of epileptic etiology, consistent with spike-wave stupor. Therefore, even in the presence of a clearly defined metabolic disorder, triphasic waves on the EEG may not be due to metabolic encephalopathy; they may reflect an epileptic state precipitated by the metabolic disorder.

Combination of infarctions in the posterior inferior cerebellar artery and anterior spinal artery territories.

After an episode of vasodilator-induced systemic hypotension, a 75-year-old man developed ocular lateropulsion to the right, left-side-dominant quadriparesis, loss of superficial sensation below C4 dermatome level, and anuresis. Magnetic resonance imaging (MRI) showed infarcts in the right cerebellar hemisphere (posterior inferior cerebellar artery territory) and the upper cervical cord (anterior spinal artery territory); the combination of posterior inferior cerebellar artery (PICA) and anterior spinal artery (ASA) infarcts has not been reported previously. Angiography revealed severe stenosis in the bilateral vertebral arteries. Hemodynamic hypoperfusion of the stenotic vertebral arteries may cause this unusual combination.