Incidence of thrombosis in Japanese patients with Fabry disease

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Abstracts / Journal of the Neurological Sciences 283 (2009) 240–320

diabetes mellitus for one year, and complex partial seizures for 3 months. Neurological examination was performed after the postictal confusional mental state had passed. There was mental retardation, a limited conjugate vertical gaze, and bilateral hearing loss. Muscle power was 4/5 in proximal muscle groups of all limbs. Deep tendon reflexes were absent. Plantar reflexes were bilaterally downgoing. Cerebral magnetic resonance imaging showed subacute infarcts in cortical and subcortical areas of the left temporal lobe and a subacute subdural hematoma in the left temporo-occipital region. A biopsy from the biceps muscle was performed, and ragged-red fibers were seen in a Gomori trichrome stain. The second patient; A 20 year-old right handed male was admitted with lethargy and left hemiparesis. In past history, he had convulsion for three months. In neurologic examination; left hemiparesis (muscle power was 1/5). Deep tendon reflexes were hypoactive in left side. Plantar reflex was positive in left side. Cerebral magnetic resonance imaging showed acute-subacute infarct at left anterior frontal, temporo-parietal and posterior occipital region. Ragged-red fibers were seen in a Gomori trichrome stain. In following up; sensorineural deafness and aprosodia were determined. Conclusions: To the best of our knowledge, subdural hematoma is an unusual finding and aprosodia is rare in MELAS. Clinicians seeing these rare patients should consider subdural hematoma as a cause of stroke-like symptoms. doi:10.1016/j.jns.2009.02.227

Epidemiology and clinical characteristics of occipital brain infarct in young adults in Southwestern Finland M.H. Martikainen, K. Majamaa Department of Neurology, University of Turku, Turku, Finland Background and aims: Previous studies have suggested a frequency of 10% for mitochondrial disorder in young patients with stroke. We studied the epidemiology and clinical characteristics of occipital brain infarct in young adults in Southwestern Finland. We aim to determine the frequency of mitochondrial disease among young adults with occipital brain infarct. Methods: We reviewed the medical charts of Turku University Central Hospital during the years 1987–2005. We identified 619 patients, aged 18– 45 years, with ICD-9 or ICD-10 diagnoses of brain infarct or visual field loss. Patients with an occipital brain infarct or a homonymous hemianopia or quadrantanopia were then ascertained. Results: 49 patients (31 women) fulfilled the selection criteria. Seven (one woman) were deceased. The clinical characteristics of the patients are shown in Table 1. We used the Mitochondrial Disease General Criteria (MDC) to evaluate the probability of mitochondrial disease among the patients based on the available medical chart information. Five patients (10%) scored four points suggesting a clinically possible mitochondrial disease. We requested a blood sample for later genetic analysis from the 42 living patients and received 27 blood samples. Conclusions: Migraine seems to be more common in young patients with occipital brain infarct than in the general population, especially among women. The MDC scores alone were not sufficient for a definite diagnosis of a mitochondrial disease. Mitochondrial DNA of the patient samples will be analyzed for mutations in future studies.

Table 1 Clinical characteristics of young patients with occipital brain infarct. total n

49

age (mean ± SD)

33.6 ± 8.0

living men 12

living women 30

35.9 ± 9.3 32.4 ± 7.2 infarct in CT or MRI 48 (98%) 12 29 (97%) (100%) migraine 13 (27%) 1 (8.3%) 12 (40%) smokers 20(41%) 4 (33%) 14 (47%) oral contraceptives 11(35% of women) n.a 11 (37%)

doi:10.1016/j.jns.2009.02.228

deceased men 6

deceased women 1

33.8 ± 9.2 6 (100%)

41 1 (100%)

1 (17%) 2 (33%) n.a.

0 0 0

A young male patient affected by Anderson–Fabry's disease presenting recurrent strokes. A case report S. Buechnera, W. Borsinib a Department of Neurology, Regional General Hospital, Bolzano, Bozen, Italy b Department of Neurological Sciences, Careggi Hospital, Florence, Italy Background: Anderson–Fabry's disease (AFD) is a rare, X-linked lysosomal storage disorder secondary to deficiency of alpha-galactosidase A (α-GAL A). This results in progressive glycosphingolipid accumulation throughout the body, causing systemic vasculopathy and multisystem disease. Cerebrovascular complications such as transitory ischemic attacks (TIAs) and strokes are common in AFD with a young age of onset. Aims: We describe a male AFD patient who suffered from recurrent strokes leading to severe morbidity and cognitive impairment at a young age. Material and methods: A young male AFD patient whose α-GAL A activity was 0.01 nmol/mg/h presented with relapsing TIAs an ischemic strokes since the age of 27, besides antiplatelet and anticoagulant treatment and enzyme replacement therapy for 1 year. In adolescence he had suffered from episodic, painful acroparesthesias and skin angiokeratomas and he had bilateral cornea verticillata. Over the years the patient developed mild proteinuria and very mild hypertrofic cardiomyopathy. Results: The recurrent strokes provoked significant disability in the patient characterized by tetraplegia, bulbar symptoms, autonomic and cognitive deficits and death at the age of 37. Brain MRI demonstrated multiinfarctual encephalopathy, leucoaraiosis, and cerebral atrophy compatible with smallvessel disease. Conclusion: We reported an unusual case of a young AFD patient who presented predominantly with cerebrovascular manifestations instead of the clinical features of classic AFD seen in most hemizygous males. Investigations for common and rare risk factors for stroke (e.g. nicotine abuse, diabetes mellitus, arterial hypertension, severe cardiopathy, coaguloathies, vasculitis and CADASIL) were negative. AFD should be considered in young patients with stroke if an etiologic diagnosis is not reached after complete investigations. Recurrent strokes cause significant disability in young age, including cognitive impairment. doi:10.1016/j.jns.2009.02.229

Incidence of thrombosis in Japanese patients with Fabry disease K. Utsumi, Y. Kamada, M. Yamazaki, Y. Komaba, K.I. Katsura, Y. Iino, Y. Katayama, M. Watanabe Department of Internal Medicine, Divisions of Neurology, Nephrology, and Rheumatology, Nippon Medical School, Tokyo, Japan Background and aims: Fabry disease is an X-linked lysosomal storage disease resulting from deficient activity of the enzyme a_galactosidase (aGal) A. The accumulation of globotriaosylceramide in the endotherial cells of blood vessels may lead to thrombosis of the brain and other tissues. Recently, safety and effectiveness of recombinant a-Gal A replacement therapy for Fabry disease have been reported. A high incidence of thrombotic accidents in Fabry disease has been postulated. However, a systemic study on thrombosis in cases of Fabry disease has not been undertaken. Methods: To clarify the incidence of thrombosis in Fabry disease, we undertook a systemic study on thrombosis in patients with Fabry disease including hemizygous males and heterozygous females. We screened 65 patients with Fabry disease (49 hemizygotes and 16 heterozygotes) from 39 unrelated Japanese families. Fabry disease was diagnosed on the basis of the clinical signs and symptoms, family pedigree, and a-Gal A activity. Results: We found that ten patients with Fabry disease (7 hemizygous males and 3 heterozygous females) had experienced thrombotic accidents, and before age 40 years in 6 cases. All 10 patients had classic Fabry disease. Nine of these thrombotic patients developed brain infarctions, including one man who had the complication of recurrent thrombophlebitis. The remaining woman showed central retinal artery occlusion and thrombophlebitis. There were no other potential etiological factors for the development of thrombosis, such as atrial fibrillation, diabetes mellitus, hypertension and hyperlipidemia.

Abstracts / Journal of the Neurological Sciences 283 (2009) 240–320

Conclusions: We demonstrated a high incidence of thrombosis in Fabry disease (15%). Thrombotic accidents occurred not only in hemizygous males but also in heterozygous females. The complication of thrombotic accidents should be taken into account in patients with Fabry disease. This disease should also be considered as a cause of unexplained thrombotic accidents, especially in young patients.

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Clinical, neuropsychological and neuroimaging features of mixed dementia O.S. Levin, N.A. Unishchenko, M.A. Dudarova, L.A. Batukaeva Department of Neurology, Russian Medical Academy of Postgraduate Education, Moscow, Russia

doi:10.1016/j.jns.2009.02.230

Mixed dementia: A prospective cohort study N.M. Mikhaylova Alzheimer's Disease Department, Mental Health Research Center RAMS, Moscow, Russia Alzheimer's disease associated with cerebrovascular disease is now considered the most frequent type of dementia. The aim is to study psychopathological features and clinical evolution of mixed cases of dementia with Alzheimer’s and vascular brain affection. 66 patients with mixed dementia were admitted to a day-clinic at the Moscow Alzheimer’s disease center in 2005–2006. Two control groups made up 26 patients with vascular dementia and 31 patients with Alzheimer's disease without vascular risk factors. MRI, neuropsychological examination, EEG-mapping, ultrasonography of intracranial vessels and APO E genotyping are used. The cases of mild and moderate dementia are included. Male/female ratio is different in comparative groups. Mixed dementia is four times more frequent in females since m/f ratio in VaD and AD is 1:2. Mean age for the moment of the first examination is 74.9 years for mixed cases, 74.4 years is for patients with VaD and 70.1 years for patients with AD. Mixed dementia had more frequent late onset than in cases of VaD and AD. Mild dementia is more common in patients with VaD. Non-cognitive neuropsychiatric disorders are presented in 51.5% of mixed dementia, in 46.9% of AD and in 65.3% of VaD. Confusional episodes with delirious symptoms are equally frequent in mixed dementia and vascular dementia (resp., 36.4% and 34.6%), but much more rare in pure AD (7.7%). Transient ischemic brain attacks were in history of 46% in VaD cases and in 13% of mixed dementia since were absent in AD cases. MRI picture is very different in three groups of patients. Ventricular and subarachnoidal space enlargement was common, but signs of leukoaraiosis as well as number and localization of vascular focal changes are very various. There are differences in neurotransmitters, neuroprotective and vasoactive treatment response.

Objective: Vascular risk factors simultaneously contribute to cerebrovascular disease (CVD) and Alzheimer's disease (AD). Therefore it is natural, that CVD and AD often coexist. However, clinical, neuropsychological and neuroimaging characteristics of mixed dementia (MD), the role of vascular and degenerate components in its pathogenesis remain poorly studied. Methods: We evaluated 14 patients with AD (according NINCDS-ADRDA criteria), 15 patients with vascular dementia (VD, according NINDS-AIREN criteria) and 16 patients with clinically diagnosed MD. Diagnosis of MD was established according to following criteria: 1) the presence of clinical and neuropsychological features of AD, 2) the presence of clinical and/or neuroimaging features of CVD. All patients participating in the study had mild dementia (MMSE score was 18 or higher). A comprehensive battery of neuropsychological tests and MRI (0.5 T scan) was used for evaluation of the patients. Results: Patients with VD and MD had worse attention and psychomotor functions than patients with AD (p < 0.05). There were no distinctions between 3 groups on delayed recall in memory tests, but recognition scores in patients with AD and MD was lower than in patients with VD (p < 0.05). The number of semantic associations (verbal fluency test) in patients with MD and AD were lower than in patients with VD, but there were no differences on phonetic or grammatical associations. Patients with MD occupied an intermediate position between patients with AD and VD on white matter lesions, lacunae and territorial infarcts scores. The degree of hippocampus atrophy in patients with AD and MD was higher than in patients with VD (p < 0.05). Conclusion: Patients with MD occupy an intermediate position between AD and VD on neuropsychological and neuroimaging parameters. Nevertheless, the majority of patients with MD is closer to AD patients on the neuropsychological profile or the degree of hippocampus atrophy. doi:10.1016/j.jns.2009.02.233

Behavioral changes caused by diencephalic lesion

doi:10.1016/j.jns.2009.02.231 K.C. Chung, S.B. Lee, K.C. Park, T.B. Ahn, S.S. Yoon, D.I. Chang Department of Neurology, KyungHee University Hospital, Seoul, South Korea Vascular dementia: Cortical dysfunction as functional misbalance of living system hierarchy U.B. Lushchyk, V.V. Novytskyy Scientific Medical Center, Kiev, Ukraine For the last years, an interest in dementia rose significantly in the psychoneurolofical practice. The tendency may be connected with the fact that the ages of patients contingent with the disease are becoming younger in many European countries. We were surprised when we received official information about small piece (nearly 5%) of vascular dementia among all kinds of dementias. Our experience in past years in diagnostics and treatment of 3 patients with vascular dementia and 37 patients with elements of dementia in the content of postcomatous apallic syndrome shows that there is another point of view to this problem. USD of arterial and venous vessels (the author's method by U.B. Lushchyk) in these patients shows a similar pattern of hemodynamic disturbance on the macrolevel: severe cerebral arterial deficits, venous cerebral hypertension, and intracranial hypertension. Besides, microcirculation level of blood supply decreased considerably according to the method of smart optical Capillaroscopy. Thus, total blood supply deficiency on the macrolevel was nearly 50–70% and on the microlevel residual circulation was nearly 10% of physiological value. From the point of view of a living system's functional structure– decreasing of intravascular moving pressure with phenomenon of cerebrovascular insufficiently in cortical areas leads to cortical dysfunction. doi:10.1016/j.jns.2009.02.232

The core behavioral abnormalities of the paramedian thalamic infarct are a state of somnolence and abulia accompanied by amnesia and a ‘frontal brain’ syndrome. In addition to these findings, chronic amnesia, distractibility, hyperorality, affective dyscontrol, socially inappropriate behavior, and mood changes have been reported in some case studies. Sexual disinhibition and uncontrolled eating behavior are traditionally believed to be related to the lesion. We describe the case of the patient, who suffered a MRdocumented ischemic lesion of left paramedian thalamus. Case: A 51-year-old, right-handed female garment shopkeeper presented with diplopia, dysarthria 9 days ago. She had a history of hypertension of 2 years ago, and took the hormonal replacement therapy due to postmenopausal syndrome. No psychotic episodes were known in her family, and she had never gone through a period of mania or depression. Neurologic examination shows esotropia with impaired upward gaze, mild right hemiparesis and hemianesthesia. During the first 2 days she fall asleep more than 14 h of the day, and gradually regained consciousness. Hyperorality and manic-like state with disinhibition affecting speech with joking, laughing, inappropriate comments, and undue joviality were observed. She had a tendency of hyperactivity, euphoria, and rule-breaking behavior. Neuropsychological testing revealed: Brain MRI depicted an ischemic lesion of left mediodorsal thalamus and brain SPECT showed hypoperfusion at the left frontal cortex. Discussion in contrast to the majority of the paramedian thalamic infarct-cases who present with persistent hypersomnolence and abulia, our patient’s clinical picture was dominated by hyperactivity and a manic-like state. Her clinical findings and a SPECT-study suggest that her behavioral changes result from the dirubtion of fronto-subcortical connections, namely of the orbitofrontal loop which is