Spinal cord hemorrhage in a patient with neurosarcoidosis on long-term corticosteroid therapy: case report.

BACKGROUND: Central nervous system bleeding is a rare complication of neurosarcoidosis: only 18 cases of spontaneous cerebral hematoma have been reported. We present the first recorded case of spinal cord hemorrhage in neurosarcoidosis. CASE PRESENTATION: A 48-year-old Caucasian woman had relapsing neurosarcoidosis for 5 years, with inflammatory spinal and cerebral lesions. While on 20 mg corticosteroids, she experienced subacute paraparesia with right leg pain. A spine MRI revealed a low thoracic hematomyelia at the T10-T11 level. Despite high doses of corticosteroids, her condition continued to worsen. Surgical evacuation of the hematoma was performed 10 days after the onset of bleeding, and she partially recovered. CONCLUSION: This report highlights the possibility of spinal cord hemorrhage secondary to sarcoid vasculitis. The patient improved after surgical evacuation of the intramedullary hematoma. Immuno-modulating agents must be envisaged in severe neurosarcoidosis, to prevent complications.

Lyme borreliosis in southern United Kingdom and a case for a new syndrome, chronic arthropod-borne neuropathy.

This series of serologically confirmed Lyme disease is the largest reported in the UK and represents 508 patients who presented to one hospital in the South of England between 1992 and 2012. The mean rate of borreliosis throughout this period was 9·8/100,000 population, much higher than the reported national rate of 1·7/100,000. The actual rate increased each year until 2009 when it levelled off. Patients clinically presented with rash (71%), neurological symptoms (16%, of whom half had VII cranial nerve palsies), arthropathy (8%), pyrexia (5%), cardiac abnormalities (1%) or other manifestations (<1%). Twenty percent of patients had additional non-specific symptoms of fatigue, myalgia, and cognitive changes. Serological diagnosis was with a two-tiered system of ELISA and immunoblot. There was a marked seasonal presentation in the summer months and in the first and sixth decades of life. A third of patients gave a clear history of a tick bite. The median interval between tick bite and clinical symptoms was 15 days [interquartile range (IQR) 9-28 days], with a further interval of 14 days to clinical diagnosis/treatment (IQR 2-31 days). Most cases were acquired locally and only 5% abroad. Patients responded to standard antibiotic therapy and recurrence or persistence was extremely rare. A second group of patients, not included in the clinical case series, were those who believed they had Lyme disease based on a probable tick bite but were seronegative by currently available validated tests and presented with subjective symptoms. This condition is often labelled chronic Lyme disease. These patients have a different disease from Lyme disease and therefore an alternative name, chronic arthropod-borne neuropathy (CAN), and case definition for this condition is proposed. We suggest that this chronic condition needs to be distinguished from Lyme disease, as calling the chronic illness 'Lyme disease' causes confusion to patients and physicians. We recommend research initiatives to investigate the aetiology, diagnosis and therapy of CAN.

Juvenile xanthogranulomas of the nervous system: A report of two cases and review of the literature.

Juvenile xanthogranulomas (JXG) are uncommon non-Langerhans cell histiocytic proliferations which arise most often in children. While most cases present as solitary cutaneous lesions, occasional cases involve extracutaneous sites. Rare examples of JXGs have been reported involving all levels of the neuroaxis. We present two cases of JXGs involving the nervous system, and review the literature. The first patient was a 14-year-old female with headaches and a mass involving the left trigeminal nerve; pathologic examination showed a JXG. At 11 months follow-up, after administration of systemic chemotherapy, the patient remained stable with residual tumor. The second patient was a 15-year-old female with leg weakness and numbness, who underwent complete surgical resection of a dural JXG. At eight months follow-up, she showed no evidence of tumor, and was able to walk without difficulty. Review of the literature revealed 38 previously published reports of JXGs involving the nervous system. The CNS was involved in the majority (75%) of cases. The clinical characteristics of JXGs arising in the CNS varied significantly from cases in the peripheral nervous system (PNS); CNS tumors occurred in younger patients, more often males, and were more likely to be associated with concurrent cutaneous and extra-nervous systemic lesions. The clinical outcomes were similar for CNS and PNS lesions, with the caveat that all three lethal JXGs occurred in the CNS. The clinical and radiologic presentation of JXGs is nonspecific, thus necessitating biopsy and pathologic examination to arrive at the diagnosis. The pathologic differential diagnosis includes a heterogeneous group of histiocytic proliferations; immunostaining for histiocytic markers CD68, factor XIIIa, and Fascin, and the absence of Birbeck granules and CD1a immunoexpression suggests the diagnosis of JXG. In many cases, total surgical resection is curative. However, some cases will require additional chemotherapy and/or radiotherapy.

[The early comprehensive rehabilitation of the children with perinatal pathology of the craniovertebral region and cerebrospinal neurological symptoms].

This paper is designed to report the results of a clinical study of the children presenting with neurologic pathology for the detection of the most common concomitant craniovertebral disorders. In addition, the experience of application of the methods for comprehensive rehabilitation is presented with special reference to remedial exercises, manual therapy, massage, and other physiotherapeutic procedures. Positive experience with the application of orthopedic devices is described including the Shants collars and corsets as well as the observance of the specific orthopedic locomotor regimen. These combined measures are designed to enhance the quality of life of the patients, correct their neurologic symptoms, and improve the compromised academic performance.

Successful treatment of monomorphic primary central nervous system post-transplantation lymphoproliferative disorder 5 years after kidney transplantation.

A 31-year-old man underwent living-related kidney transplantation in 2004 as a consequence of primary focal segmental glomerulosclerosis (FSGS). Four years after the transplantation, we confirmed nephrotic syndrome caused by recurrent FSGS. We performed plasmapheresis and low-density lipoprotein adsorption. We also combined steroid therapy with a reduction in the dose of tacrolimus and an increased dose of mycophenolate mofetil. The nephrotic syndrome improved dramatically with this combined therapeutic approach. However, 10 months after these treatments, he revisited our hospital because of altered consciousness. We detected multiple tumor masses in his brain that were ring enhanced on contrast magnetic resonance imaging. Consequently, we suspected primary central nervous system post-transplantation lymphoproliferative disorder (CNS-PTLD). We performed a craniotomy to biopsy the brain tumors. The biopsy specimen showed Epstein-Barr virus-associated diffuse large B-cell lymphoma. There is no definitive treatment for CNS-PTLD. Therefore, we treated the primary CNS-PTLD successfully with whole-brain radiation and discontinuation of immunosuppression therapy.

Tuberculosis of the central nervous system in immunocompromised patients: HIV infection and solid organ transplant recipients.

Central nervous system (CNS) tuberculosis (TB) is a devastating infection with high rates of morbidity and mortality worldwide and may manifest as meningitis, tuberculoma, abscess, or other forms of disease. Immunosuppression, due to either human immunodeficiency virus infection or solid organ transplantation, increases susceptibility for acquiring or reactivating TB and complicates the management of underlying immunosuppression and CNS TB infection. This article reviews how immunosuppression alters the clinical presentation, diagnosis, treatment, and outcome of TB infections of the CNS.

Neurosarcoidosis mimicking acute cervical disc prolapse.

We describe the case of a 29-year-old farmer who developed upper limb radiculopathy followed by myelopathy in his lower limbs. MRI findings suggested cervical disc prolapse with cord changes. Despite a successful anterior cervical decompression and fusion his symptoms rapidly returned. Further investigations ultimately diagnosed underlying neurosarcoidosis.

[A patient with neurosarcoidosis presenting with easy falling and dysphagia].

A 68-year-old woman was referred to our hospital for progressive dizziness, gait disturbances and weight loss for 18 months. The patient was alert and showed dysphagia and a marked tendency to fall backward. Electronystagmography showed bilateral vestibular dysfunction and audiometry showed right sensorineural hearing disturbance. Cerebrospinal fluid exam showed mononuclear pleocytosis and elevated protein levels. On 18F-FDG PET/CT, abnormal uptake was observed in the mediastinal lymph nodes, from which biopsy specimens were obtained. Histological findings showed non-caseous granuloma and a diagnosis of bilateral vestibulocochlear, glossopharyngeal and vagal nerve palsies due to neurosarcoidosis was made. Steroid therapy resulted in improvement in her clinical symptoms. Neurosarcoidosis should be included in the differential diagnosis of patients showing progressive easy falling and dysphagia.

Neuroprotective effects of anthocyanins and its major component cyanidin-3-O-glucoside (C3G) in the central nervous system: An outlined review.

Anthocyanins, a class of water soluble flavonoids extracted from plants like berries and soybean seed, have been shown to display obvious anti-oxidative, anti-inflammatory, and anti-apoptotic activities. They are recommended as a supplementation for prevention and/or treatment of disorders ranging from cardiovascular disease, metabolic syndrome, and cancer. In the central nervous system (CNS), anthocyanins and its major component cyanidin-3-O-glucoside (C3G) have been reported to produce preventive and/or therapeutic activities in a wide range of disorders, such as cerebral ischemia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and glioblastoma. Both anthocyanins and C3G can also affect some important processes in aging, including neuronal apoptosis and death as well as learning and memory impairment. Further, the anthocyanins and C3G have been shown to prevent neuro-toxicities induced by different toxic factors, such as lipopolysaccharide, hydrogen peroxide, ethanol, kainic acid, acrolein, glutamate, and scopolamine. Mechanistic studies have shown that inhibition of oxidative stress and neuroinflammation are two critical mechanisms by which anthocyanins and C3G produce protective effects in CNS disorder prevention and/or treatment. Other mechanisms, including suppression of c-Jun N-terminal kinase (JNK) activation, amelioration of cellular degeneration, activation of the brain-derived neurotrophic factor (BDNF) signaling, and restoration of Ca2+ and Zn2+ homeostasis, may also mediate the neuroprotective effects of anthocyanins and C3G. In this review, we summarize the pharmacological effects of anthocyanins and C3G in CNS disorders as well as their possible mechanisms, aiming to get a clear insight into the role of anthocyanins in the CNS.

A review for the pharmacological effect of lycopene in central nervous system disorders.

Lycopene is an aliphatic hydrocarbon carotenoid extracted from plants like tomatoes, papayas, and watermelons. Previous studies have shown that lycopene can exert prophylactic and/or therapeutic effects in different disorders, such as heart failure and neoplasm via anti-oxidative, anti-inflammatory, and anti-proliferative activities. In the central nervous system (CNS), lycopene also has prophylactic and/or therapeutic effects in different type of disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), cerebral ischemia, epilepsy, and depression. Lycopene also improves cognition and memory ability of rodents in different pathological conditions, such as diabetes, colchicine exposure, high-fat diet (HFD), and aging. Further, lycopene can prevent neuro-toxicities induced by monosodium glutamate (MSG), trimethyltin (TMT), methylmercury (MeHg), tert-butyl hydroperoxide (t-BHP), and cadmium (Cd). In some special conditions such as ethanol addiction and haloperidol-induced orofacial dyskinesia, lycopene administration displays special therapeutic effects. Mechanisms including inhibition of oxidative stress and neuroinflammation, inhibition of neuronal apoptosis, and restoration of mitochondrial function have been shown to mediate the neuroprotective effects of lycopene. Other mechanisms, such as inhibition of nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK), activation of the nuclear factor erythroid 2-related factor (Nrf2) and brain-derived neurotrophic factor (BDNF) signaling, and restoration of intracellular Ca2+ homeostasis, may be also involved in the neuroprotective effect of lycopene. In hope of get a clear impression about the role of lycopene in the CNS, we summarize and discuss the pharmacological effects of lycopene as well as its possible mechanisms in CNS disorder prevention and/or therapy.

Secondary intracranial hypertension with acute intracranial pressure crisis in superficial siderosis.

Superficial siderosis of the central nervous system is a very rare disease related to hemosiderin deposits in the brain, brainstem, cerebellum and spinal cord due to chronic subarachnoid hemorrhage. Chronic increased intracranial pressure develops in about one-third of affected cases. We report a patient with superficial siderosis and sudden intracranial pressure crisis. A 29-year-old man experienced a subacute episode of headache, tinnitus and blurred vision. Magnetic resonance imaging of the brain revealed hemosiderin deposits characteristic of superficial siderosis. Extensive diagnostic work-up excluded causative pathologies of bleeding. Lumbar puncture and continuous intra-ventricular cerebrospinal fluid (CSF) pressure monitoring revealed continuous CSF pressure increase. Implantation of a ventriculo-peritoneal shunt led to complete clinical recovery. Our case emphasizes that patients with superficial siderosis may present with sudden elevation of intracranial pressure due to chronic intracranial hypertension. In this situation permanent CSF drainage provides a useful therapeutic option.

[Operative case of eosinophilic granuloma of the skull with dural invasion].

Eosinophilic granuloma is the localized form of Langerhans' cell histiocytosis. There are several reports of magnetic resonance (MR) imaging of eosinophilic granuloma of the skull, however there are few reports about dural enhancement. We report an operative case of eosinophilic granuloma of the skull with dural invasion. A 42-year old man was admitted to our hospital. He was neurologically intact and there were no other osseous or soft tissue lesions. CT showed an osteolytic lesion in the left parietal bone. MR images showed the lesion as isointense on T1-weighted, and high intense on T2-weighted images. T1-weighted images with Gd-DTPA demonstrated the mass which was enhanced with dural surface and subgaleal tissue. The angiogram demonstrated a tumor stain fed by the left occipital artery. Bone scintigraphy demonstrated a solitary lesion showing peripheral uptake with a central defect. The patient underwent craniectomy with removal of the dura and a subgaleal lesion. Histological examination revealed characteristic eosinophilic granuloma with dural invasion. No recurrence of the lesion was demonstrated 6 months after surgery.

Insulin receptor in the brain: Mechanisms of activation and the role in the CNS pathology and treatment.

While the insulin receptor (IR) was found in the CNS decades ago, the brain was long considered to be an insulin-insensitive organ. This view is currently revisited, given emerging evidence of critical roles of IR-mediated signaling in development, neuroprotection, metabolism, and plasticity in the brain. These diverse cellular and physiological IR activities are distinct from metabolic IR functions in peripheral tissues, thus highlighting region specificity of IR properties. This particularly concerns the fact that two IR isoforms, A and B, are predominantly expressed in either the brain or peripheral tissues, respectively, and neurons express exclusively IR-A. Intriguingly, in comparison with IR-B, IR-A displays high binding affinity and is also activated by low concentrations of insulin-like growth factor-2 (IGF-2), a regulator of neuronal plasticity, whose dysregulation is associated with neuropathologic processes. Deficiencies in IR activation, insulin availability, and downstream IR-related mechanisms may result in aberrant IR-mediated functions and, subsequently, a broad range of brain disorders, including neurodevelopmental syndromes, neoplasms, neurodegenerative conditions, and depression. Here, we discuss findings on the brain-specific features of IR-mediated signaling with focus on mechanisms of primary receptor activation and their roles in the neuropathology. We aimed to uncover the remaining gaps in current knowledge on IR physiology and highlight new therapies targeting IR, such as IR sensitizers.

Melatonin in Pregnancy: Effects on Brain Development and CNS Programming Disorders.

Melatonin is an important neuroprotective factor and its receptors are expressed in the fetal brain. During normal pregnancy, maternal melatonin level increases progressively until term and is highly transferred to the fetus, with an important role in brain formation and differentiation. Maternal melatonin provides the first circadian signal to the fetus. This indolamine is also produced de novo and plays a protective role in the human placenta. In pregnancy disorders, both maternal and placental melatonin levels are decreased. Alteration in maternal melatonin level has been associated with disrupted brain programming with long-term effects. Melatonin has strong antioxidant protective effects directly and indirectly via the activation of its receptors. The fetal brain is highly susceptible to oxygenation variation and oxidative stress that can lead to neuronal development disruption. Based on that, several approaches have been tested as a treatment in case of pregnancy disorders and melatonin, through its neuroprotective effect, has been recently accepted against fetal brain injury. This review provides an overview about the protective effects of melatonin during pregnancy and on fetal brain development.

[Effects of prophylactic treatment of central nervous system leukemia in children. Analysis of CNS prophylactic treatment with cyclic high dose multichemotherapy, craniospinal irradiation, and high dose infusion of MTX].

Thirty-five children with previously untreated ALL or AUL who received CNS prophylactic therapy with 8 treatment regiments were analyzed. After eutering complete remission, patients received CNS-prophylaxis with one of the following regimens: Group A- cyclic high dose multichemotherapy plus intermittent intrathecal methotrexate (MTX); Group B-craniospinal irradiation plus intermittent intrathecal MTX; Group C-intermittent high dose intravenous MTX. Incidence of CNS-leukemia and bone marrow relapse was less frequent in Group B. EEG abnormalities were seen in 38.5% of Group A, 40% of Group B, and 28.6% of Group C respectively, but the abnormalities were transient. IQs of three groups were above 100, but IQs of CNS-leukemia patients, especially VIQs had a tendency to be low.

Neuroprotective potential of silymarin against CNS disorders: insight into the pathways and molecular mechanisms of action.

Silymarin, a C25 containing flavonoid from the plant Silybum marianum, has been the gold standard drug to treat liver disorders associated with alcohol consumption, acute and chronic viral hepatitis, and toxin-induced hepatic failures since its discovery in 1960. Apart from the hepatoprotective nature, which is mainly due to its antioxidant and tissue regenerative properties, Silymarin has recently been reported to be a putative neuroprotective agent against many neurologic diseases including Alzheimer's and Parkinson's diseases, and cerebral ischemia. Although the underlying neuroprotective mechanism of Silymarin is believed to be due to its capacity to inhibit oxidative stress in the brain, it also confers additional advantages by influencing pathways such as ß-amyloid aggregation, inflammatory mechanisms, cellular apoptotic machinery, and estrogenic receptor mediation. In this review, we have elucidated the possible neuroprotective effects of Silymarin and the underlying molecular events, and suggested future courses of action for its acceptance as a CNS drug for the treatment of neurodegenerative diseases.

Two patients with audiovestibular sarcoidosis.

We report two patients with biopsy-proven audiovestibular sarcoidosis who presented with hearing loss, vertigo and gait ataxia. Oto-neurological investigations confirmed the presence of sensorineural hearing loss, vestibular hypofunction and abnormal auditory brainstem responses. MRI scans of the brain revealed enhancement of the vestibulo-cochlear nerves. Both patients responded to high dose oral corticosteroid treatment, although one patient has required multiple trials of immunosuppressant drug therapy because of relapsing disease.