Apamin Enhances Neurite Outgrowth and Regeneration after Laceration Injury in Cortical Neurons.

Apamin is a minor component of bee venom and is a polypeptide with 18 amino acid residues. Although apamin is considered a neurotoxic compound that blocks the potassium channel, its neuroprotective effects on neurons have been recently reported. However, there is little information about the underlying mechanism and very little is known regarding the toxicological characterization of other compounds in bee venom. Here, cultured mature cortical neurons were treated with bee venom components, including apamin, phospholipase A2, and the main component, melittin. Melittin and phospholipase A2 from bee venom caused a neurotoxic effect in dose-dependent manner, but apamin did not induce neurotoxicity in mature cortical neurons in doses of up to 10 µg/mL. Next, 1 and 10 µg/mL of apamin were applied to cultivate mature cortical neurons. Apamin accelerated neurite outgrowth and axon regeneration after laceration injury. Furthermore, apamin induced the upregulation of brain-derived neurotrophic factor and neurotrophin nerve growth factor, as well as regeneration-associated gene expression in mature cortical neurons. Due to its neurotherapeutic effects, apamin may be a promising candidate for the treatment of a wide range of neurological diseases.

The protective effect of nnano-selenium against cadmium-induced cerebellar injury via the heat shock protein pathway in chicken.

Cadmium (Cd) is one of the toxic environmental heavy metals that poses health hazard to animals due to its toxicity. Nano-Selenium (Nano-Se) is a Nano-composite form of Se, which has emerged as a promising therapeutic agent for its protective roles against heavy metals-induced toxicity. Heat shock proteins (HSPs) play a critical role in cellular homeostasis. However, the potential protective effects of Nano-Se against Cd-induced cerebellar toxicity remain to be illustrated. To investigate the toxic effects of Cd on chicken's cerebellum, and the protective effects of Nano-Se against Cd-induced cerebellar toxicity, a total of 80 male chicks were divided into four groups and treated as follows: (A) 0 mg/kg Cd, (B) 1 mg/kg Nano-Se (C) 140 mg/kg Cd + 1 mg/kg Nano-Se (D) 140 mg/kg Cd for 90 days. We tested heat shock protein pathway-related factors including heat shock factors (HSFs) HSF1, HSF2, HSF3 and heat shock proteins (HSPs) HSP10, HSP25, HSP27, HSP40, HSP60, HSP70 and HSP90 expressions. Histopathological results showed that Cd treatment caused degradation of Purkinje cells. In addition, HSFs and HSPs expression decreased significantly in the Cd group. Nano-Se co-treatment with Cd enhanced the expression of HSFs and HSPs. In summary, our findings explicated a potential protective effect of Nano-Se against Cd-induced cerebellar injury in chicken, suggesting that Nano-Se is a promising therapeutic agent for the treatment of Cd toxicity.

Oleoylethanolamide Delays the Dysfunction and Death of Purkinje Cells and Ameliorates Behavioral Defects in a Mouse Model of Cerebellar Neurodegeneration.

Oleoylethanolamide (OEA) is an endocannabinoid that has been proposed to prevent neuronal damage and neuroinflammation. In this study, we evaluated the effects of OEA on the disruption of both cerebellar structure and physiology and on the behavior of Purkinje cell degeneration (PCD) mutant mice. These mice exhibit cerebellar degeneration, displaying microtubule alterations that trigger the selective loss of Purkinje cells and consequent behavioral impairments. The effects of different doses (1, 5, and 10 mg/kg, i.p.) and administration schedules (chronic and acute) of OEA were assessed at the behavioral, histological, cellular, and molecular levels to determine the most effective OEA treatment regimen. Our in vivo results demonstrated that OEA treatment prior to the onset of the preneurodegenerative phase prevented morphological alterations in Purkinje neurons (the somata and dendritic arbors) and decreased Purkinje cell death. This effect followed an inverted U-shaped time-response curve, with acute administration on postnatal day 12 (10 mg/kg, i.p.) being the most effective treatment regimen tested. Indeed, PCD mice that received this specific OEA treatment regimen showed improvements in motor, cognitive and social functions, which were impaired in these mice. Moreover, these in vivo neuroprotective effects of OEA were mediated by the PPARα receptor, as pretreatment with the PPARα antagonist GW6471 (2.5 mg/kg, i.p.) abolished them. Finally, our in vitro results suggested that the molecular effect of OEA was related to microtubule stability and structure since OEA administration normalized some alterations in microtubule features in PCD-like cells. These findings provide strong evidence supporting the use of OEA as a pharmacological agent to limit severe cerebellar neurodegenerative processes.

Bow Hunter's Syndrome.

Bow hunter's syndrome is due to vertebrobasilar insufficiency caused by rotational compression of the vertebral artery. We report a case in which an osteophyte compressed the left vertebral artery causing cerebellar stroke. The patient underwent successful resection of the osteophyte via anterior surgical approach, and his symptoms of headache and dizziness dissipated postoperatively. This unique syndrome has been treated with multiple modalities and must remain in the clinician's differential as a treatable cause of stroke.

Case Report: A Case of Severe Cryptococcal Immune Reconstitution Inflammatory Syndrome Presenting with Brain and Intradural Abscesses in an HIV Patient.

Clinical worsening or new manifestation of cryptococcal disease following initiation of anti-retroviral therapy (ART) in an HIV patient is a hallmark of cryptococcal immune reconstitution inflammatory syndrome (C-IRIS). However, it can be difficult to distinguish IRIS from worsening or new infection. Here, we present a case of severe C-IRIS involving multiple cerebellar, spinal, and intradural abscesses and spinal arachnoiditis 7 months after ART initiation in an AIDS patient with uncertain prior ART compliance. He had multiple prior episodes of cryptococcal meningitis with complications necessitating ventriculoperitoneal shunt placement and was on suppressive fluconazole when he developed worsening brain manifestations. He received empiric anti-cryptococcal re-induction without improvement. All cerebrospinal fluid cultures remained sterile, with negative Cryptococcus PCR testing, and his condition continued to worsen prior to corticosteroid initiation. Ultimately, C-IRIS was diagnosed by brain biopsy. This case demonstrates an extreme in severity of C-IRIS and in the timeline of presentation after ART initiation.

Autoimmune Vestibulocerebellar Syndromes.

Autoimmune disorders affecting the vestibular end organs, vestibular pathways, vestibular nuclei, and vestibulocerebellum are often underrecognized as a cause of chronic dizziness and ataxia. Autoantibodies specific for cell-surface, synaptic, and intracellular neural antigens serve as biomarkers of these disorders. This article describes the epidemiology, clinical presentation, diagnostic considerations, imaging findings, treatment, and prognosis of autoimmune disorders, in which the vestibulocerebellar syndrome is the main or presenting clinical presentation. Antibodies specific for intracellular antigenic targets described in the article are PCA-1 (Purkinje cell cytoplasmic antibody type 1, also known as anti-Yo), ANNA-1 (antinuclear neuronal antibody type 1, also known as anti-Hu), ANNA-2 (antinuclear neuronal antibody type 2, also known as anti-Ri), Ma1/2 (anti-Kelch-like 11/12 antibody), Kelch-like 11, amphiphysin, CV2 (collapsin response 2, also known as collapsin response mediator protein-5 [CRMP5]), VGCC (voltage-gated calcium channel), GAD65 (glutamic acid decarboxylase 65-kDa isoform), AP3B2 (adaptor protein 3B2, also known as anti-Nb), MAP1B (microtubule-associated protein 1B antibody, also known as anti-PCA-2), and neurochondrin antibodies. Antibodies targeting cell-surface or synaptic antigenic targets described in the article include DNER (delta/notchlike epidermal growth factor related receptor; antigen to anti-Tr), CASPR2 (contactin-associated proteinlike 2), septin-5, Homer-3, and mGluR1 (metabotropic glutamate receptor 1). The vestibulocerebellar presentation is largely indistinguishable among these conditions and is characterized by subacute onset of cerebellar symptoms over weeks to months. The diagnosis of autoimmune vestibulocerebellar syndromes is based on a combination of clinical and serological features, with a limited role for neuroimaging. Subtle eye movement abnormalities can be an early feature in many of these disorders, and therefore a meticulous vestibulo-ocular examination is essential for early and correct identification. Cancer occurrence and its type are variable and depend on the autoantibody detected and other cancer risk factors. Treatment comprises immunotherapy and cancer-directed therapy. Acute immunotherapies such as intravenous immunoglobulin, plasma exchange, and steroids are used in the initial phase, and the use of long-term immunosuppression such as rituximab may be necessary in relapsing cases. Outcomes are better if immunotherapy is started early. The neurologic prognosis depends on multiple factors.

Epicrania Fugax as the presenting symptom of a cerebellar abscess.

BACKGROUND: Epicrania fugax is included in the appendix of the International Classification of Headache Disorders and is characterized as recurrent brief attacks of linear or zigzag pain moving across the cranial surface, commencing and terminating in the distribution of different nerves. We present a new case of epicrania fugax in which the headache was the presenting symptom of a cerebellar abscess. CASE REPORT: We present a 58-year-old woman with prior history of Chiari I malformation who underwent suboccipital craniectomy. Two weeks after surgery, she experienced paroxysmal pain episodes of 1-3 seconds, with constant linear trajectory from the right occipital surface to the right orbital region, remaining pain free between episodes. Cranial tomography showed a hypodense intraaxial lesion in the right cerebellar hemisphere. Magnetic Resonance Imaging exhibited intralesional bleeding and peripheral enhancement after gadolinium administration. Post-surgical cerebellar abscess was diagnosed and antibiotic therapy was started; the patient underwent urgent surgical drainage. Pain disappeared after the surgery and the patient remains pain free with 12 months of follow-up. CONCLUSION: Posterior fossa abnormalities have been described as a possible cause of secondary epicrania fugax. The presence of red flags should encourage conducting of paraclinical tests to rule out a symptomatic form.

Advances in Therapies of Cerebellar Disorders: Immune-mediated Ataxias.

The identification of an increasing number of immune mediated ataxias suggests that the cerebellum is often a target organ for autoimmune insults. The diagnosis of immune mediated ataxias is challenging as there is significant clinical overlap between immune mediated and other forms of ataxia. Furthermore the classification of immune mediated ataxias requires further clarification particularly for those ataxias where no specific antigenic trigger and associated antibodies have been identified. Recognition of immune mediated ataxias remains imperative as therapeutic interventions can be effective, although given the relative rarity of this entity, large-scale treatment trials may not be feasible. This review will discuss advances in therapies for immune mediated ataxias based on what is currently available in the literature.

Acute cerebellitis caused by herpes simplex virus

Case presentation of acute cerebellitis caused by herpes simplex virus.

Cerebellar abscesses, infective endocarditis and bacteraemia due to a rare pathogen: Streptococcus constellatus.

Intracranial infections may result from contiguity, such as mastoiditis or acute otitis media, or from haematogenous dissemination from an infectious source. Streptococcus constellatus, a coccus from the normal genital, oral and gastrointestinal flora, has a tendency to form abscesses, but not to cause infective endocarditis (IE). Also, S. constellatus is an extremely rare causative agent of brain abscess. We report the case of a woman with a colorectal tumour who presented with IE and cerebellar abscesses due to a S. constellatus bacteraemia.

Laser Acupuncture at HT7 Improves the Cerebellar Disorders in Valproic Acid-Rat Model of Autism.

The novel therapeutic strategy against autism is essential due to the limited therapeutic efficacy. Based on the benefit of laser acupuncture at HT7 acupoint on the neurological disorders related with oxidative stress and inflammation, its benefit on oxidative stress, neuroinflammation, and GABAergic/glutamatergic imbalance in cerebellum of autism have been considered. To elucidate this issue, male rat pups were induced autistic-like conditions by valproic acid (VPA) and treated with laser acupuncture at HT7 acupoint once daily between postnatal Day 14 and Day 40. At the end of study, the changes of oxidative stress markers, the expressions of cytokines interleukin 6 (IL-6) and glutamic acid decarboxylase (GAD) proteins (65 kDa and 67 kDa) together with gamma-aminobutyric acid transaminase (GABA-T) activity and density of Purkinje cell in the cerebellum were assessed. The results showed that laser acupuncture HT7 decreased oxidative stress, IL-6 expression, and GABA-T activity but increased the expressions of GAD 65 kDa together with the density of Purkinje cells in the cerebellum. Therefore, laser acupuncture at HT7 is the potential strategy to improve the cerebellar disorders in VPA-rat model of autism. The mechanism may occur partly via the decrease of oxidative stress status, inflammation, and the improved GABAergic function.

Cryptococcal cerebellitis in no-VIH patient / Cerebelitis criptococócica en paciente VIH negativo

Abstract Introduction: Cryptococcosis is an opportunistic fungal infection whose etiology is Cryptococcus neofromans / C. gattii, complex which affects immunocompromised patients mainly. Meningeal infection is one of the most common presentations, but cerebellar affection is rare. Case Description: Male patient with 65 old years, from an area of subtropical climate with chronic exposure to poultry, without pathological antecedents, who presented clinical picture consistent with headache, fever, seizures and altered mental status. Clinical findings and diagnostic methods: Initially without menigeal signs or intracranial hypertension and normal neurological examination. Later, the patient developed ataxia, dysdiadochokinesia and limb loss. By lumbar punction and image of nuclear magnetic resonance (NMR) cerebellitis cryptococcal was diagnosticated. Treatment: Antifungal therapy with amphotericin B and fluconazole was performed, however the patient died. Clinical Relevance: The cryptococcosis has different presentations, it´s a disease whose incidence has been increasing since the advent of the HIV / AIDS pandemy, however the commitment of the encephalic parenchyma and in particular the cerebellum is considered rare. In this way we are facing the first case of cryptococcal cerebellitis in our midst.

Resumen Introducción: La Criptococosis es una infección micótica oportunista cuya etiología es el complejo Cryptococcus neofromans/C. gattii, el cual principalmente afecta pacientes inmunocomprometidos. La afección meníngea es una de las formas más frecuentes pero el compromiso cerebeloso es raro. Descripción del Caso: Paciente masculino de 65 años, procedente de un área rural con exposición crónica a aves de corral, sin antecedentes patológicos, con cuadro clínico inicial consistente en cefalea crónica, fiebre, convulsiones y alteración del estado mental. Hallazgos clínicos y métodos diagnósticos: Al principio sin signos de hipertensión intracraneana ni meníngeos y examen neurológico normal, con posterior desarrollo de ataxia, disdiadococinesia y dismetría. Se diagnosticó Cerebelitis Criptocococica con ayuda de repetidos estudios de LCR y resonancia magnética nuclear. Tratamiento: Se inició terapia antifúngica con Anfotericina B y Fluconazol, con respuesta tórpida y el paciente fallece. Relevancia clínica: La Cerebelitis Criptocococica es una presentación clínica infrecuente que requiere sospecha clínica y recursos diagnósticos para definir el tratamiento de forma temprana. La inmunosupresión no es requisito para padecer esta infección.

The Complex Diagnostic Challenge in Children With Non-Central Nervous System Cancer and Cerebellar Mutism.

Multiple etiologies should be considered in the differential diagnosis of immunocompromised patients with non-central nervous system cancer and viral infections who develop mutism. Acute cerebellitis, caused by infections or by neurotoxicity resulting from chemotherapy; paraneoplastic cerebellar degeneration; atypical posterior reversible encephalopathy syndrome; and acute disseminated encephalomyelitis may all cause mutism in such patients. This condition warrants prompt recognition and may require treatment with immunotherapy, as it may be an immune-mediated process. We present 2 patients with leukemia and viral illness who developed cerebellar mutism in the setting of acute cerebellitis and responded to immunotherapy, suggesting that the condition involved a parainfectious immune-mediated response.

Sudden benzodiazepine-induced resolution of post-operative pediatric cerebellar mutism syndrome: a clinical-SPECT study.

Post-operative pediatric cerebellar mutism syndrome (PPCMS) is a clinical syndrome arising from cerebellar injury and characterized by absence of speech and other possible symptoms and signs. Rare reports described some benefit after administration of dopamine agonist therapy, but no treatment has proven efficacy. In this paper, we report on the dramatic, sudden resolution of PPCMS induced by midazolam administration in a boy who underwent posterior fossa surgery for choroid plexus papilloma of the fourth ventricle. In addition to clinical improvement, post-midazolam single-photon emission computed tomography also demonstrated amelioration of brain perfusion.

Next-Generation Sequencing for Diagnosis and Tailored Therapy: A Case Report of Astrovirus-Associated Progressive Encephalitis.

A boy with X-linked agammaglobulinemia experienced progressive global motor decline, cerebellar syndrome, and epilepsy. All standard polymerase chain reactions for neurotropic viruses were negative on cerebrospinal fluid and brain biopsy. Next-generation sequencing allowed fast identification of a new astrovirus strain (HAstV-VA1/HMO-C-PA), which led to tailor the patient's treatment, with encouraging clinical monitoring over 1 year.

Acute pseudotumoral hemicerebellitis in a child: a rare and distinct entity?

A pseudotumoral presentation of acute hemicerebellitis is rare in pediatric age. The authors report a new single case study of a 7-year-old child with pseudotumoral unilateral cerebellitis mimicking an intracranial tumor, which clinically presented itself with signs of intracranial hypertension and mild contralateral hemiparesis, completely recovered after anti-inflammatory therapy. Brain magnetic resonance imaging (MRI) was essential for the differential diagnosis between inflammatory and neoplastic processes. The literature highlighting specific clues about pseudotumoral hemicerebellitis as a distinct clinical and radiological entity is reviewed.

Non-stiff anti-amphiphysin syndrome: clinical manifestations and outcome after immunotherapy.

Amphiphysin antibody causes paraneoplastic stiff-person syndrome and can also result in a variety of neurological manifestations. Here, we investigated the clinical spectrum of 20 patients with non-stiff anti-amphiphysin syndrome and their responses to immunotherapy. The most common neurological manifestation was limbic encephalitis (n=10), followed by dysautonomia (n=9), and cerebellar dysfunction (n=6). Cancer was detected in only seven patients. Intravenous immunoglobulin or steroid treatment was effective in most patients, but three improved only after rituximab treatment. Our study suggests that anti-amphiphysin syndrome can manifest as non-stiff encephalomyelitis and is only partially associated with cancer. Active immunotherapy, including rituximab, would be beneficial.

[Tuberculoma mimicking the tumor of ponto-cerebellum angle as complication after postvaccinated tuberculous otitis media]. / Poszczepienne gruzlicze zapalenie ucha srodkowego i jego powiklania - opis przypadku.

INTRODUCTION: Tuberculosis is a major problem of constant importance all over the world. Notably, in the developed countries it is due to immunosuppressive therapy and AIDS. Primary otological tuberculosis constitutes a very small share of cases of this disease. Moreover, the appearance of tuberculomas remains unique to even greater extent. CASE REPORT: Clinical history of a patient who has already been infected tuberculosis for 60 years in result of the BCG vaccination. Ponto-cerebellum angle tumour appeared in his brain as complication ensuing the disease. The first therapeutic method used was based on antituberculous drugs, subsequent surgical intervention (cerebello-pontine angle tumor removal via translabirynthin approche) was necessary however. We suspected another cause of this lesion - cholesteatoma or facial nerve neurinoma. Correct diagnosis give only histopatological examination. Because of facial nerve palsy, facial nerve reconstruction was necessary (connection of n. VII and n. XII) CONCLUSION: This case reminds us that correct diagnosis of tuberculosis remains a serious problem despite the long experience and the development of diagnostics and treatment methods. Nowadays we observe the unusual clinical manifestations of the disease (e.g. such as ear pain, tinnitus, rapid hearing loss) more frequently.