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Distribution of cranial MRI abnormalities in patients with symptomatic and subclinical CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, inherited cause of early stroke and dementia, with a poor prognosis. This study was performed to clarify lesion appearance and pattern of lesion distribution in CADASIL. 20 members of a single family were tested for the CADASIL gene mutation and studied with cranial MRI. Scans were evaluated for lesion load and pattern of lesion distribution. 19 patients had cranial MRI, of whom 11 had normal MRI scans, were clinically unaffected and tested negative for the CADASIL gene mutation. The remaining eight patients had abnormal cranial MRI scans: seven patients were positive for the CADASIL gene mutation and one (untested) patient was severely clinically affected. Three of the patients who tested positive for the CADASIL gene mutation were clinically unaffected at the time of imaging. All eight patients with abnormal cranial MRI had subcortical white matter abnormalities, mostly in frontal and temporal lobes. Lesions involving the corpus callosum were present on sagittal T2 weighted images in four of five clinically affected and one of three clinically unaffected patients. Lesions involving the deep grey nuclei and the brain stem were common. On T1 weighted images, lesions were either poorly defined (confluent white matter hypointensity) or well defined (cystic infarcts or enlarged perivascular spaces). Atrophy was infrequent. Familiarity with the range of cranial MRI appearances may aid diagnosis of CADASIL. Recognition of cranial imaging features in asymptomatic CADASIL patients could prompt earlier diagnosis.

Adult↗

Opercular cheiro-oral syndrome.

Perioral and distal upper limb sensory dysfunction (cheiro-oral syndrome) has classically been attributed to cortical involvement. In previously reported cases of the syndrome, caused by stroke, however, the thalamus or brain stem has been the actual site of the lesion. We have studied two patients with infarct in the superficial middle cerebral artery territory involving the parietal operculum. Sensory involvement was purely subjective in the face, but severe hypoesthesia was present in the distal upper limb, involving mainly position sense, stereognosis, and graphesthesia. Temperature and pain sensation were involved in one patient. These findings correlated with involvement of the lower part of the postcentral gyrus, more caudal parts of the parietal operculum, and underlying white matter. This opercular cheiro-oral syndrome seems more uncommon than faciobrachiocrural hemihypesthesia associated with anterior parietal artery territory infarct. A double supply to the parietal opercular region through branches of the temporal arteries and anterior parietal artery may explain the rarity of cheiro-oral syndrome resulting from hemisphere stroke, because simultaneous and partial compromise to two different pial artery networks is uncommon.

Aged↗

Neuronal differentiation of transplanted embryonic stem cell-derived precursors in stroke lesions of adult rats.

Stroke represents one of the leading causes of death and disability in Western countries, but despite intense research, only few options exist for the treatment of stroke-related infarction of brain tissue. In experimental stroke, cell therapy can partly reverse some behavioural deficits. However, the underlying mechanisms have remained unknown as most studies revealed only little, if any, evidence for neuronal replacement and the observed behavioural improvements appeared to be related rather to a graft-derived induction of a positive response in the remaining host tissue than to cell replacement by the graft itself. The present study was performed to test a murine embryonic stem cell (ESC)-based approach in rats subjected to endothelin-induced middle cerebral artery occlusion. Efficacy of cell therapy regarding graft survival, neuronal yield and diversity, and electrophysiological features of the grafted cells were tested after transplanting ESC-derived neural precursors into the infarct core and periphery of adult rats. Here, we show that grafted cells can survive, albeit not entirely, most probably as a consequence of an ongoing immune response, within the infarct core for up to 12 weeks after transplantation and that they differentiate with high yield into immunohistochemically mature glial cells and neurons of diverse neurotransmitter-subtypes. Most importantly, transplanted cells demonstrate characteristics of electrophysiologically functional neurons with voltage-gated sodium currents that enable these cells to fire action potentials. Additionally, during the first 7 weeks after transplantation we observed spontaneous excitatory post-synaptic currents in graft-derived cells indicating synaptic input. Thus, our observations show that ESC-based regenerative approaches may be successful in an acutely necrotic cellular environment.

Animals↗

[Possibilities of investigation and clinical application of adult human stem cells].

Multipotent adult tissue stem cells have high plasticity and transdifferentiation ability. The stem cell therapy can be the solution of curing many severe diseases such as osteogenesis imperfecta, hepatic failure, heart muscle damage after myocardial infarction, I-type diabetes, variety of central nervous system disorders such as brain injury, stroke, Parkinson's disease and other neurodegenerative disorders. Isolation of certain types of stem cells is solved nowadays, but low frequency of these cells and lack of special identification markers make their isolation and search more difficult. The more and more developed in vitro cell culture technologies, the widespread macromolecule amplification and examination techniques of molecular biology and the gene technology tools for genetic modification of stem (and other) cells contribute to research and therapeutic applications of stem cells. Transfer of new genetic material to stem cells and expression of the gene product in daughter cells--because missing or damaged genes can be replaced--is an exiting approach of the treatment of congenital (enzyme deficiencies) and acquired human diseases (cancers).

Adult↗

[Peculiar forms of benign tumors of the brain stem].

Three patients are described, who were treated because of tumors of the medulla oblongata, growing towards the lumen of the IV ventricle and into the subarachnoid space. In two cases clinical cure was achieved after partial removal of the tumor and radiotherapy. One of these patients 32 years after the operation is working as a librarian, the other one treated 25 years ago is also professionally active and has a 5-year old son. In the third case only fragments of the tumor were taken for histological examination but radiotherapy was not given in view of serious condition of the patient. The patient however improved and after 23 years he died suddenly from myocardial infarction. On the base of these cases and a survey of the world literature it may by supposed that there are two kinds of brain stem tumors differing in their clinical course and direction of growth. Type A develops in the transverse plane of the brain stem and along its longitudinal axis producing paralysis of cranial nerves, signs of damage to the long ascending and descending pathways and disturbances of equilibrium. Symptoms of intracranial hypertension appear late or not at all. Type B grows into the lumen of the fourth ventricle and subarachnoid space as well, without infiltrating the deep structures of the brain stem. Partial removal of the tumor followed by radiotherapy may give useful survival for many years and may be even permanent cure.

Adolescent↗

Utility of perfusion-weighted CT imaging in acute middle cerebral artery stroke treated with intra-arterial thrombolysis: prediction of final infarct volume and clinical outcome.

BACKGROUND AND PURPOSE: The goal of this study was to evaluate the utility of perfusion-weighted CT (PWCT) in predicting final infarct volume and clinical outcome in patients with acute middle cerebral artery (MCA) stroke. METHODS: Twenty-two consecutive patients with MCA stem occlusion who underwent intra-arterial thrombolysis within 6 hours of stroke onset had noncontrast CT and CT angiography with whole-brain PWCT imaging before treatment. Infarct volumes were computed from the initial PWCT and follow-up scans; clinical outcome was measured with the modified Rankin scale. RESULTS: Initial PWCT lesion volumes correlated significantly with final infarct volume (P=0.0002) and clinical outcome (P=0.01). For the 10 patients with complete recanalization, the relationship between initial and final lesion volume was especially strong (R(2)=0.94, P<0.0001, slope of regression line=0.92). For those without complete recanalization, there was progression of lesion volume on follow-up imaging (R(2)=0.50, P=0.01, slope of regression line=1.61). All patients with either initial PWCT lesion volumes >100 mL or no recanalization had poor outcomes (Rankin scores, 4 to 6). Mean admission NIH Stroke Scale scores and mean lesion volumes in the poor outcome group were significantly different compared with the good or fair outcome (Rankin scores, 0 to 3) group (21+/-4 versus 17+/-5, P=0.05, and 106+/-79 versus 29+/-37 mL, P=0.01). Patients with initial volumes <100 mL and partial or complete recanalization all had good (Rankin scores, 0 to 2) or fair (Rankin score, 3) outcomes. CONCLUSIONS: Lesion volumes on admission PWCT images approximate final infarct volume for patients with early complete recanalization of MCA stem occlusion. For those without complete recanalization, there is subsequent enlargement of lesion volume on follow-up. Initial PWCT lesion volumes also have predictive value; volumes >100 mL are associated with a poor clinical outcome. In these highly selected patients, initial PWCT lesion volume was a stronger predictor of clinical outcome than was initial NIH Stroke Scale score.

Acute Disease↗

Surgical management of acute cerebellar infarction.

After reviewing the literature, a personal series of 10 adult patients with cerebellar infarction diagnosed by CT scan is described. The clinical picture in young adult men is characterized by rapid onset of headache, vomiting, vertigo, ataxia and blurred vision. After this sudden onset the patients may present a stable course or a rapid or delayed onset of brain stem compression, revealed by impairment of consciousness. CT scan is the diagnostic method of choice. The correlation between angiographic and CT localization of the infarction is not good. For therapy the following policy is suggested: in alert and clinically stable patients: medical treatment (mannitol, glycerol, dexamethason), ICP and serial CT monitoring; in alert patients with hydrocephalus or mass effect: medical treatment and monitoring as mentioned before; ventricular drainage if ICP surpasses 350 mm H2O; in patients with impaired consciousness and hydrocephalus or mass effect: immediate ventricular drainage. If it is not followed by prompt improvement of the level of consciousness, an emergency suboccipital craniectomy with removal of the infarcted tissue should be done.

Adult↗

Silent cerebral microbleeds on T2*-weighted MRI: correlation with stroke subtype, stroke recurrence, and leukoaraiosis.

BACKGROUND AND PURPOSE: Gradient-echo T2*-weighted MRI is uniquely sensitive to detect silent, old hemosiderin deposits, but the clinical significance of such "microbleeds" remains to be determined. Therefore, we investigated the incidence and the number of microbleeds among different stroke subtypes and the correlation with stroke recurrence and the severity of leukoaraiosis. METHODS: This study consisted of 213 patients (73.5+/-9.1 years old, 104 men and 109 women), who were classified according to stroke subtypes into atherothrombotic infarction (24 patients), cardioembolic infarction (23 patients), lacunar infarction (66 patients), intracerebral hemorrhage (35 patients), and control (65 patients) groups. Gradient-echo T2*-weighted MRI was performed with a 1.5 T system, and asymptomatic microbleeds were located and counted. RESULTS: The incidence and the number of microbleeds were significantly greater in patients with intracerebral hemorrhage (71.4% and 9.1+/-13.8, respectively) and lacunar infarction (62.1% and 7.4+/-16.1) compared with patients with cardioembolic infarction (30.4% and 2.5+/-5.6), atherothrombotic infarction (20.8% and 0.63+/-1.53), and controls (7.7% and 0.09+/-0.34). There was a correlation between the number of microbleeds and the severity of periventricular hyperintensity (r=0.626, P<0.0001). There was also a correlation between the number of microbleeds and the number of intracerebral hemorrhages (r=0.689, P<0.0001) or lacunar infarctions (r=0.514, P<0.0001). The locations of microbleeds were subcortical white matter (31.8%), thalamus (24.8%), basal ganglia (19.8%), brain stem (12.0%), and cerebellum (11.7%). CONCLUSIONS: The findings suggest that microbleeds on T2*-weighted MRI are an indicator of advanced small artery disease of the brain with an increased risk for bleeding. This result should be taken into consideration when treating patients with stroke, and further studies are required.

Aged↗

[A case of SSPE that showed watershed infarction like image on MRI initially, and progressed to whole brain atrophy].

We reported a 15-year-old male patient of subacute sclerosing panencephalitis (SSPE), progressed from stage I to stage IV. On his admission, his clinical state was stage I with disturbance of generalized attention, myoclonus of upper limbs and no focal cortical signs. After rapid progression to stage III in a month, his clinical state became fairly stable and gradually advanced to stage IV. We followed him with serial CT and MR images. On imagings we found initial lesion in left parietoocipital lobe and spread in right parietoocipital lobe, anterior lobe and then brain stem, showing low density on plain CT scans and high intensity of T2 weighed MR images. This initial lesion situated in watershed area was hardly distinguishable from watershed infarction. In addition, we found blood flow decrease in vertebral artery system with SPECT and Doppler flowmetry. These findings suggested vascular pathogenesis of SSPE. We showed the imaging processes of SSPE progression from formation of initial lesion to demyelination and gliosis of total brain.

Adolescent↗

Posterior circulation infarcts in patients with vertebrobasilar dolichoectasia.

BACKGROUND AND PURPOSE: Vertebrobasilar dolichoectasia (VBD) may produce symptoms by direct compression of cranial nerves or the brain stem, by obstructive hydrocephalus, or by ischemia in the vertebrobasilar arterial territory. This study was undertaken to examine and characterize clinical and imaging findings in patients with stroke associated with VBD and compare these data with those for patients with VBD who did not have a stroke. METHODS: We studied 40 consecutive stroke patients with associated VBD. All were evaluated by CT scan (n=9), MRI (n=6), or both (n=25). The diameter of the basilar artery (BA), height of bifurcation, and transverse position were evaluated. Clinical and imaging findings were compared with those found in a group of 40 VBD patients without stroke. RESULTS: More than half of the patients (24 of 40) had infratentorial infarcts, located mainly in the midpons. Sixteen patients had supratentorial lesions localized in the thalamus (n=8) or in the superficial arterial territory of the posterior cerebral artery (PCA; n=8). The diameter and height of the bifurcation of the BA were correlated with the location of the lesion (PCA territory versus BA territory), in that severe ectasia and vertical elongation of the BA were significantly more often observed in patients with infarcts in PCA territory than in patients with infarcts in territories supplied by branches of the BA. Comparison of VBD patients with and without stroke showed that the incidence of arterial hypertension and the degree of ectasia and lateral displacement of the BA were not significantly different in the two groups. Patients with stroke more often had atherosclerotic changes of the posterior circulation (P=.0006) and a higher degree of vertical elongation of the BA (P=.025). CONCLUSIONS: In patients with VBD, superimposed atheromatous changes of the posterior circulation may have an important role in precipitating ischemia. However, other factors related to the severity of the dolichoectasia also favor ischemia and in some cases are the only factors responsible.

Aged↗

[Cerebellar infarct. Clinical presentation and x-ray computed tomography of the brain].

A series of 12 patients with cerebellar infarcts diagnosed by computerized tomography are reviewed. The clinical features of cerebellar infarctions cover a wide spectrum, mimicking symptoms and signs from an acute labyrinthitis to a rapidly expanding posterior fossa mass lesion with brain stem and cerebral dysfunction. Two patients were asymptomatic and three showed signs of cerebellar dysfunction only. Three patients had evidence of brain stem dysfunction with cranial nerve palsies accompanying the cerebellar deficit. Two presented a pseudovestibular form with sudden onset of nausea, vomiting, rotary dizziness and ataxia. A pseudotumoral form with intracranial hypertension was found in two cases, in which softening tissue acts as a rapidly expanding posterior foss mass lesion. It is difficult to identify the exact artery involved in a cerebellar infarct because of the collateral circulation and connections between the three major arteries. Atherosclerosis and general decrease in blood flow can be regarded as the most likely factors precipitating focal cerebellar infarction. Surveillance is necessary during the first days with anti-edematous therapy. Rapid deterioration of consciousness should be considered a sign of increasing intracranial pressure progressing with the development of hydrocephalus. If necessary, surgical decompression by external drainage or by direct access to the posterior fossa can be carried out.

Cerebellar Ataxia↗

Postoperative brainstem and cerebellar infarcts.

OBJECTIVE: To study the clinical features and causes of postoperative brainstem and cerebellar infarcts. METHODS: Two groups were studied. The 10 group 1 patients had cardiac (eight) or aortic (two) surgery. The 12 group 2 patients had noncardiac-nonvascular surgery, including orthopedic (five), gynecologic (four), and general (three). Patients were studied by stroke services at university hospitals in Boston (13), Charlottesville (three), Baltimore (three), and Mainz (three) during 2 consecutive years. RESULTS: Onset of strokes was immediately postoperative (six), during the first 48 postoperative hours (nine), and delayed 3 days or more (seven). Clinical syndromes were altered level of consciousness or cognition (15), vestibulocerebellar (four), and hemiparesis with focal brainstem signs (three). Infarction involved the brainstem (13), cerebellum (13), and posterior cerebral artery hemispheric territory (10). Causes: In group 1, five infarcts were due to cardiogenic embolism and three to embolism from the aorta. One patient had a postoperative pontine lacunar infarct and one developed an infarct in the territory of a known stenotic basilar artery. In group 2, one patient had vertebral artery injury from instrumentation, one had medical complications with severe hemorrhage and hypotension, and 10 most likely had position-related vertebral artery thromboses. CONCLUSIONS: Patients with postoperative brainstem and cerebellar infarcts present with altered consciousness or vestibulocerebellar syndromes. The major cause of brain infarcts after cardiac surgery is embolism from the heart and aorta. The causes of infarction after general surgery are less clear, but neck positioning during or after surgery may play an important role by promoting thrombi in compressed arteries that later embolize intracranially when neck motion becomes free.

Adolescent↗