Isolated axial lateropulsion caused by an acute lateral medullary infarction involving the dorsal spinocerebellar tract: A case report.

Lateral medullary syndrome encompasses a broad spectrum of symptoms and signs depending on the bulbar localization of the lesion. Body lateropulsion (BL) can occur without vestibular and cerebellar symptoms, as a unique manifestation of a lateral medullary infarction. However, it is relatively rare and challenging to diagnose. We report a case of a 72-year-old woman who presented with a tendency to fall to the right. She denied having vertigo, cerebellar signs, sensory loss, or motor weakness. No signs of vestibular dysfunction were found on the ENT examination. Neurological evaluation was unremarkable, except for mild ataxia of the right limbs along with BL to the right side when standing and walking. Brain magnetic resonance (MR) imaging showed an acute small infarct in the right lateral aspect of the medulla extending from the rostral to the caudal level. MR angiography found no stenosis or vascular occlusions. We believe that ipsilateral axial lateropulsion shown by our patient may be related to a selective ischemic lesion of the dorsal spinocerebellar tract in its medullary course. A lateral medullary infarction should be seriously considered in patients who present with isolated BL without further signs of bulbar involvement.

Trends of recanalization therapies and state of art for ischemic stroke treatment in Campania region, Italy.

BACKGROUND: According to the last Italian report by the Ministry of Health in 2018, the estimated number of acute ischemic strokes (AIS) in Campania is 10,000/year, with an expected number of 1390 intravenous thrombolysis (IVT) and 694 mechanical thrombectomies (MT). In 2017, only 1.5% of expected patients received IVT and 0.2% MT. This study analyzed the trend of IVT and MT in 2019-2020 and depicted the state of art of Stroke Care in Campania. METHODS: From the regional health task force, we obtained the hospital discharge forms from all private and public hospitals in Campania; we selected patients with a principal diagnosis of AIS and measured the rate of patients admitted to neurology units and the rate of IVT, MT, and IVT + MT for both 2019 and 2020. RESULTS: In 2019, we observed 4817 admissions for AIS; 2858/4817 (59.3%) patients were admitted to neurology units. Out of 4817 patients, 192 received IVT, 165 MT, and 131 IVT + MT (488 treated patients; 10.1%). In 2020, we observed 4129 admissions for AIS; 2502/4129 (62.7%) patients were admitted to neurology units. Out of 4129 patients, 198 received IVT, 250 MT, and 180 IVT + MT (628 treated patients; 15.2%). These results showed that despite a reduction of AIS admissions in 2020, the relative and absolute rate of recanalization treatments increased. However, the number of patients who were not admitted to neurology units nor received acute treatments remained dramatically high. CONCLUSION: Despite the development of acute treatments, the Campania Stroke Network still needs significative efforts to improve.

Forgetting the Unforgettable: Transient Global Amnesia Part II: A Clinical Road Map.

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a temporary memory disorder with profound anterograde amnesia and a variable impairment of the past memory. Usually, the attacks are preceded by a precipitating event, last up to 24 h and are not associated with other neurological deficits. Diagnosis can be challenging because the identification of TGA requires the exclusion of some acute amnestic syndromes that occur in emergency situations and share structural or functional alterations of memory circuits. Magnetic Resonance Imaging (MRI) studies performed 24-96 h after symptom onset can help to confirm the diagnosis by identifying lesions in the CA1 field of the hippocampal cornu ammonis, but their practical utility in changing the management of patients is a matter of discussion. In this review, we aim to provide a practical approach to early recognition of this condition in daily practice, highlighting both the lights and the shadows of the diagnostic criteria. For this purpose, we summarize current knowledge about the clinical presentation, diagnostic pathways, differential diagnosis, and the expected long-term outcome of TGA.

Forgetting the Unforgettable: Transient Global Amnesia Part I: Pathophysiology and Etiology.

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a temporary memory disorder with a profound anterograde amnesia and a variable impairment of the past memory. Since the first description, dating back over 60 years, several cases have beenreported in the literature. Nevertheless, TGA remains one of the most mysterious diseases in clinical neurology. The debate regarding the etiology of this disease has focused mainly on three different mechanisms: vascular (due to venous flow changes or focal arterial ischemia), epileptic, and migraine related. However, to date there is no scientific proof of any of these mechanisms. Furthermore, the demonstration by diffusion-weighted MRI of lesions in the CA1 field of the hippocampus cornu ammonis led us to hypothesize that the selective vulnerability of CA1 neurons to metabolic stress could play a role in the pathophysiology of TGA. In this review, we summarize current knowledge on the anatomy, vascularization and function of the hippocampus. Furthermore, we discuss the emerging theories on the etiology and the pathophysiological cascade leading to an impairment of hippocampal function during the attacks.

Posterior circulation ischaemic stroke-a review part I: anatomy, aetiology and clinical presentations.

Posterior circulation ischaemia is a clinicopathological condition with complex symptomatology associated with an infarction within the vertebrobasilar arterial system. Posterior circulation strokes account for about 20-25% of all ischemic strokes and remain a significant cause of patient disability and mortality. Diagnosis can be challenging because presenting symptoms are often non-focal and because there is a substantial overlap in symptoms and signs of ischaemia in the anterior circulation. Despite better imaging techniques, diagnosis and treatment of life-threatening conditions, such as basilar artery occlusions, are often delayed. Therefore, early detection of symptoms and causes of posterior circulation ischaemia is essential for choosing the most appropriate therapy. In this review, we summarise the anatomy, aetiology, typical presentations and characteristic findings of common strokes resulting from disease in the vertebrobasilar arterial system.

Posterior circulation ischemic stroke-a review part II: imaging and acute treatment.

Posterior circulation strokes affect the vertebrobasilar arterial system, account for about 20-25% of all ischemic strokes, and are a significant cause of patient disability and mortality. Diagnosis can be challenging; clinical presentation and common pitfalls facing posterior circulation stroke have been discussed elsewhere. In the first part of the review, we focus on the imaging, discussing the information that can be gathered through a correct selection and interpretation of different possible studies helping to achieve an early diagnosis and to select the best medical treatment. In the second part of the review, we will discuss the best therapeutic treatments available at the moment for posterior circulation ischemia.

Cerebral Venous Thrombosis and Headache--A Case-Series.

BACKGROUND: Headache happens in the majority of patients with Cerebral Venous Thrombosis (CVT) being sometimes the sole manifestation of the disease. Herein we report a case-series of CVT, focusing on headache characteristics. METHODS: Etiological, clinical, and radiological features of 25 consecutive adult patients with CVT were compiled from August 2005 to December 2013. Diagnosis of CVT was confirmed by brain magnetic resonance imaging and magnetic resonance venography. All patients underwent extensive systematic etiological and genetic work-up at admission. A structured questionnaire about the characteristics of headache was responded by all participants. RESULTS: Headache was reported by 23 out of 25 (92%) of participants, being by far the most frequent symptom. It was the sole manifestation in nearly one third of the patients (8/25, 32.0%). Headache was typically severe (19/23, 82.6%) and throbbing (16/23, 69.5%), with sudden onset (13/23, 56.5%) and non-remitting (20/23, 86.9%) characteristics. The sinus most frequently involved was the transverse sinus (24/25, 96.0%), either alone or in association with other sinuses. CONCLUSION: Headache is the most frequent symptom and sometimes the sole presentation of CVT.

Frataxin silencing inactivates mitochondrial Complex I in NSC34 motoneuronal cells and alters glutathione homeostasis.

Friedreich's ataxia (FRDA) is a hereditary neurodegenerative disease characterized by a reduced synthesis of the mitochondrial iron chaperon protein frataxin as a result of a large GAA triplet-repeat expansion within the first intron of the frataxin gene. Despite neurodegeneration being the prominent feature of this pathology involving both the central and the peripheral nervous system, information on the impact of frataxin deficiency in neurons is scant. Here, we describe a neuronal model displaying some major biochemical and morphological features of FRDA. By silencing the mouse NSC34 motor neurons for the frataxin gene with shRNA lentiviral vectors, we generated two cell lines with 40% and 70% residual amounts of frataxin, respectively. Frataxin-deficient cells showed a specific inhibition of mitochondrial Complex I (CI) activity already at 70% residual frataxin levels, whereas the glutathione imbalance progressively increased after silencing. These biochemical defects were associated with the inhibition of cell proliferation and morphological changes at the axonal compartment, both depending on the frataxin amount. Interestingly, at 70% residual frataxin levels, the in vivo treatment with the reduced glutathione revealed a partial rescue of cell proliferation. Thus, NSC34 frataxin silenced cells could be a suitable model to study the effect of frataxin deficiency in neurons and highlight glutathione as a potential beneficial therapeutic target for FRDA.

The THRombolysis and STatins (THRaST) study.

OBJECTIVE: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis. METHODS: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death. RESULTS: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26-2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11-1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18-2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19-0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28-0.82; p = 0.007). CONCLUSION: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.

Friedreich's ataxia: oxidative stress and cytoskeletal abnormalities.

Friedreich's ataxia (FRDA) is an autosomal recessive disorder caused by mutations in the gene encoding frataxin, a mitochondrial protein implicated in iron metabolism. Current evidence suggests that loss of frataxin causes iron overload in tissues, and increase in free-radical production leading to oxidation and inactivation of mitochondrial respiratory chain enzymes, particularly Complexes I, II, III and aconitase. Glutathione plays an important role in the detoxification of ROS in the Central Nervous System (CNS), where it also provides regulation of protein function by glutathionylation. The cytoskeletal proteins are particularly susceptible to oxidation and appear constitutively glutathionylated in the human CNS. Previously, we showed loss of cytoskeletal organization in fibroblasts of patients with FRDA found to be associated with increased levels of glutathione bound to cytoskeletal proteins. In this study, we analysed the glutathionylation of proteins in the spinal cord of patients with FRDA and the distribution of tubulin and neurofilaments in the same area. We found, for the first time, a significant rise of the dynamic pool of tubulin as well as abnormal distribution of the phosphorylated forms of human neurofilaments in FRDA motor neurons. In the same cells, the cytoskeletal abnormalities co-localized with an increase in protein glutathionylation and the mitochondrial proteins were normally expressed by immunocytochemistry. Our results suggest that in FRDA oxidative stress causes abnormally increased protein glutathionylation leading to prominent abnormalities of the neuronal cytoskeleton.

Primary myxopapillary ependymoma of the cerebellopontine angle: report of a case.

Myxopapillary ependymoma is a rare variant of ependymoma, almost exclusively occurring in the region of the cauda equina and filum terminale. We describe a myxopapillary ependymoma located in the left cerebellopontine angle of a young man suffering from peripheral vertigo and left sensorineural hearing loss for years. The patient underwent surgical removal of the tumour. Microscopic examination showed histological and immunohistochemical features consistent with a diagnosis of myxopapillary ependymoma. Imaging studies of the spine yielded normal findings, confirming the lesion's primary nature. To the best of our knowledge, this is the first case of primary intracranial myxopapillary ependymoma described in this location.

Protein glutathionylation in human central nervous system: potential role in redox regulation of neuronal defense against free radicals.

Neuronal defense against free radicals is mediated primarily by the glutathione system. A cerebral defect of this system gives rise to the oxidative stress occurring in some neurological diseases. Glutathione provides a means of regulating protein function by glutathionylation, consisting of the formation of mixed disulfides between cysteines and glutathione. The glutathionylation of proteins, during both constitutive metabolism and oxidative stress, represents for the cell a mechanism to link physiological processes, and/or adaptive stress responses, to changes in intracellular redox states. In this study, we analyzed the topographic distribution of the protein glutathionylation normally occurring in human central nervous system. Constitutively glutathionylated proteins appeared uniformly distributed throughout all cortical layers of the cerebral and cerebellar cortex as well as throughout the gray matter of the spinal cord. The degree of immunocytochemical staining was clear in neurons, mild in oligodendrocytes, and weaker in astrocytes. The proteins preferentially glutathionylated were cytoskeletal proteins. Our results suggest a potential role of glutathionylation in the redox regulation of neuronal survival and in the control of axon/dendrite stability.