Progressive Neurological Decline Research Articles

Resection of an Intramedullary Glomus-type Arteriovenous Malformation of the Conus Medullaris: Technical Note and Step-by-step Surgical Video.

Arteriovenous malformations (AVMs) of the spine include a broad spectrum of lesions that vary from a simple arteriovenous fistulous connection to a more complex net of abnormal vessels involving multiple spinal levels. These entities are poorly studied and understood because of their rarity and are often either managed conservatively with observation if the lesion is complex, or treated surgically or interventionally in the presence of an accessible and distinct fistulous connection. Most surgeons avoid intervening on more intricate lesions until they become symptomatic with progressive neurological decline.We describe the case of a 38-year-old man who presented with severe sharp back pain after an appendectomy procedure. A magnetic resonance angiogram (MRA) revealed an arteriovenous malformation of the conus medullaris, with a compact glomus-type nidus and arterial feeders originating from an enlarged artery of Adamkiewicz. The malformation was resected through a posterior midline approach, and the patient was neurologically intact at his discharge on postoperative Day 2. Follow-up angiography showed complete obliteration of the lesion. Our operative video is meant to serve as a step-by-step and systematic guide to the approach and management of conus arteriovenous spinal lesions, which can be difficult to treat.We provide a pre- and postoperative radiological description of the anomaly as well as a technical guide to the resection of a spinal vascular lesion. This video could serve as an operative guide and reference to neurosurgeons—both established and in training—when confronting similar disease processes in the future.

A Case of Intracranial Melanoma Metastasis Presenting with Arteriovenous Shunting

Melanoma metastases to the brain are highly vascular lesions and have a high predilection to haemorrhage. Due to their degree of vascularity, these lesions sometimes demonstrate arteriovenous shunting. They may even mimic separate entities such as arteriovenous malformations (AVM). We present one such case; a 32-year-old male who was transferred to our unit with acute left sided hemiparesis and slurred speech. Imaging demonstrated a large intracerebral haemorrhage (ICH) with arteriovenous shunting and presumed underlying AVM. This was initially managed conservatively, however progressive neurological decline over subsequent days necessitated surgical intervention and the hematoma was evacuated. An arterialised vein and nidus of abnormal vessels were identified intra-operatively and disconnected from feeding MCA vessels. There were no macroscopic appearances suggestive of a melanoma. The final diagnosis of metastatic melanoma was only made on histopathological analysis of the resected specimen. This case highlights the importance of sending all ICH samples for histopathological analysis regardless of appearances on imaging

Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm

To delineate the most recommendable treatment of spontaneous intracerebral hemorrhages and the indication for surgery, its timing, and the best surgical technique to be adopted case by case. Based on PubMed/MEDLINE, Embase, and the Cochrane Library databases, a systematic review of the literature was performed using as keywords the terms "spontaneous intracerebral hemorrhage," "surgical management," "medical management," "supratentorial," and "infratentorial." Because of the highest level of evidence, only randomized and nonrandomized clinical trials, meta-analyses, and comparative cohort studies reported within the last 12 years were selected. An updated and evidence-based treatment algorithm was reported also. The search initially returned 255 articles. After application of the exclusion criteria, only 19 studies were selected. According to the site and volume of the hematoma, admission Glasgow Coma Scale (GCS) score, and progressive neurologic decline, specific subgroups were identified. Surgery must be considered in patients with an admission GCS score ranging between 5 and 12 and a hematoma volume >30 mL. The best time-window has been reported to be 7-24 hours after ictus. Endoscopic surgery is recommendable for patients with a supratentorial hematoma >60 mL and with a poor GCS score (4-8). Alternative techniques, such as minimally invasive puncture and thrombolysis, may be considered for deeper hematoma. Careful selection of patients eligible for surgery is mandatory. The optimal timing falls into a time-window ranging between 7 and 24 hours after ictus. Minimal invasive techniques are valuable surgical options for patients in a poor GCS score or harboring large deep-seated hemorrhages.

Interaction Study of Antioxidants with Progressive Myoclonus Epilepsy by Molecular Docking Techniques

Progressive Myoclonus Epilepsy (PME) is a rare epilepsy syndrome caused by number of genetic disorders. This syndrome contains myoclonic seizures and chronic seizures along with progressive neurological decline. Oxidative stress can result into mild or severe form of these diseases and remain the cause of several other diseases such as cardiovascular diseases, neurological diseases, malignancies, renal disease, diabetes, inflammatory, skin diseases, aging, respiratory diseases, liver diseases, and different type of viral infection. The evaluation of the effectiveness of various, antioxidants is being targeted due to clinical, trials of several neurodegenerative diseases. In this study we have seen the effectiveness of antioxidants against Progressive Myoclonus Epilepsy disease. Docking is done using Schrodinger software, interaction studies shows that Resveratrol is potential drug against myoclonus epilepsy. Further study shows that antioxidants can be better inhibitor of myoclonus epilepsy disease.

Rapidly progressive neurologic decline and morbilliform rash presenting in a patient with lymphoma.

A 67-year-old male with past medical history of mantle cell lymphoma and atrial fibrillation presented with a truncal rash, bilateral lower extremity weakness, and confusion. Within three days of presentation, his condition rapidly deteriorated with the onset of diffuse flaccid paralysis, aphasia, and severe alteration in mental status. Initial results from serum studies, lumbar puncture, magnetic resonance imaging, and electroencephalogram were not diagnostic. However, on the ninth day after initial presentation, the West Nile Virus (WNV) immunoglobulin M antibody returned positive from the cerebrospinal fluid. West Nile Virus encephalitis is endemic worldwide, and is the most common viral encephalitis in the United States. WNV presents in a variety of ways, and the recognition by physicians is crucial due to the estimated 2-12% mortality rate and significant longterm morbidity of neuroinvasive disease. The initial management and long term prognosis are points of ongoing research. This case represents a particularly profound example of neuroinvasive WNV. Our patient made a significant recovery after his initial presentation with aggressive supportive care, however still suffers from bilateral lower extremity weakness more than a year later.

Type I Spinal Arteriovenous Fistula with Ventral Intradural Venous Drainage: A Proposal of a Modified Classification.

Objectives:Spinal arteriovenous fistula (AVF) is the most common spinal vascular lesion and constitutes an abnormal communication between a feeder artery and a draining vein. Arterialization of the venous plexus leads to venous hypertension; consequent edema and congestion of the spinal cord are associated with progressive neurological decline.Patients and Methods:In this report, we describe two unique cases of type I cervical spinal AVF, in which a radiculomeningeal artery forms an intradural fistula that drains into the ventral venous plexus.Results:Both patients underwent surgical obliteration of the fistula with complete occlusion confirmed on postoperative angiography.Conclusion:Both cases do not fit into the current classification scheme. A modified classification is proposed.

Oligodendrocyte-encoded Kir4.1 function is required for axonal integrity

Glial support is critical for normal axon function and can become dysregulated in white matter (WM) disease. In humans, loss-of-function mutations of KCNJ10, which encodes the inward-rectifying potassium channel KIR4.1, causes seizures and progressive neurological decline. We investigated Kir4.1 functions in oligodendrocytes (OLs) during development, adulthood and after WM injury. We observed that Kir4.1 channels localized to perinodal areas and the inner myelin tongue, suggesting roles in juxta-axonal K+ removal. Conditional knockout (cKO) of OL-Kcnj10 resulted in late onset mitochondrial damage and axonal degeneration. This was accompanied by neuronal loss and neuro-axonal dysfunction in adult OL-Kcnj10 cKO mice as shown by delayed visual evoked potentials, inner retinal thinning and progressive motor deficits. Axon pathologies in OL-Kcnj10 cKO were exacerbated after WM injury in the spinal cord. Our findings point towards a critical role of OL-Kir4.1 for long-term maintenance of axonal function and integrity during adulthood and after WM injury.

Visual Evoked Potentials as a Biomarker in Multiple Sclerosis and Associated Optic Neuritis

: ABSTRACT:: Multiple sclerosis (MS) is an inflammatory, degenerative disease of the central nervous system (CNS) characterized by progressive neurological decline over time. The need for better "biomarkers" to more precisely capture and track the effects of demyelination, remyelination, and associated neuroaxonal injury is a well-recognized challenge in the field of MS. To this end, visual evoked potentials (VEPs) have a role in assessing the extent of demyelination along the optic nerve, as a functionally eloquent CNS region. Moreover, VEPs testing can be used to predict the extent of recovery after optic neuritis (ON) and capture disabling effects of clinical and subclinical demyelination events in the afferent visual pathway. In this review, the evolving role of VEPs in the diagnosis of patients with ON and MS and the utility of VEPs testing in determining therapeutic benefits of emerging MS treatments is discussed.

Cystic Formation After Stereotactic Radiosurgery of Brain Metastasis.

Limited information is available on the natural history and etiology of cystic formation after stereotactic radiosurgery (SRS) for brain metastases (BM). We aimed to characterize the natural history of cyst formation after SRS of BM and analyze potential risk factors. We retrospectively reviewed 214 consecutive patients who underwent a total of 1106 SRSs for BM. Demographic, clinical, dosimetric, and magnetic resonance imaging MRI data were reviewed. Statistical analysis was accomplished using Student's t test, and univariate and multivariate logistic regression. The median patient age was 61 years (range, 19-91 years), and the median duration of follow-up was 424 days (range, 91-2934 days). Eleven cases of cyst formation (0.9% of 1106 treated lesions) were identified at SRS-treated BM sites among 9 patients (2 patients developed cysts at independent sites). The median interval between first SRS and first evidence of cyst was 218 days. Seven of the 9 patients (78%) sustained progressive cyst expansion and neurologic decline requiring steroid treatment. Four of these 7 patients (57%) experienced continued neurologic decline and needed surgical fenestration. On univariate analysis, receipt of >4 rounds of SRS was the sole variable associated with an increased risk of cyst formation (odds ratio, 16.58; P= 0.001). This association remained robust after adjusting for duration of follow-up (odds ratio, 13.59; P= 0.003). In our experience with 1106 SRS-treated cases of BM, cyst formation was a rare phenomenon. However, 1 in 3 patients who underwent >4 rounds of SRS sustained cyst formation. A high proportion (78%) of SRS-associated cysts progressively expanded and required medical or surgical treatment.

Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin.

Multiple sclerosis (MS) is a chronic autoimmune, inflammatory disease in the central nervous system (CNS) characterized by loss of oligodendrocytes, myelin axons, and neurons. Remyelination is an endogenous repair mechanism, which recovers the loss of myelin and is able to preserve functional axons. The hope is that the development of new treatments aiming at promoting remyelination will halt and potentially partially reverse the progressive neurological decline in MS. The development of such drugs requires adequate models. In this chapter, we will discuss the surgical procedure of injection of lysolecithin into ventral thoraco-lumbar spinal cord white matter of mice, which is particularly suitable for investigating remyelination using transgenic animals.

Cerebrotendinous xanthomatosis: early diagnosis on the basis of juvenile cataracts

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease characterized by a broad spectrum of clinical manifestations, including bilateral juvenile cataracts. Untreated CTX leads to progressive permanent neurologic decline and early death. Although symptoms begin in early childhood, diagnosis and replacement therapy with chenodeoxycholic acid is often delayed until adulthood. Frequently bilateral juvenile cataracts present in early childhood which provides ophthalmologists an opportunity to aid in early diagnosis and initiate treatment. We report the case of a child presenting with juvenile bilateral cataracts leading to the diagnosis of CTX. The morphology of cataracts and the effect of systemic treatment on its progression are described.

Preclinical development of a vaccine against oligomeric alpha-synuclein based on virus-like particles.

Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies. In addition to strategies using small molecules, neutralisation of the toxic oligomers by antibodies represents an attractive and highly specific strategy for reducing disease progression. Emerging active immunisation approaches using vaccines are already being trialled to induce such antibodies. Here we propose a novel vaccine based on the RNA bacteriophage (Qbeta) virus-like particle conjugated with short peptides of human a-syn. High titres of antibodies were successfully and safely generated in wild-type and human a-syn over-expressing (SNCA-OVX) transgenic mice following vaccination. Antibodies from vaccine candidates targeting the C-terminal regions of a-syn were able to recognise Lewy bodies, the hallmark aggregates in human PD brains. Furthermore, antibodies specifically targeted oligomeric and aggregated a-syn as they exhibited 100 times greater affinity for oligomeric species over monomer a-syn proteins in solution. In the SNCA-OVX transgenic mice used, vaccination was, however, unable to confer significant changes to oligomeric a-syn bioburden. Similarly, there was no discernible effect of vaccine treatment on behavioural phenotype as compared to control groups. Thus, antibodies specific for oligomeric a-syn induced by vaccination were unable to treat symptoms of PD in this particular mouse model.

TTC19 Plays a Husbandry Role on UQCRFS1 Turnover in the Biogenesis of Mitochondrial Respiratory Complex III

Loss-of-function mutations in TTC19 (tetra-tricopeptide repeat domain 19) have been associated with severe neurological phenotypes and mitochondrial respiratory chain complex III deficiency. We previously demonstrated the mitochondrial localization of TTC19 and its link with complex III biogenesis. Here we provide detailed insight into the mechanistic role of TTC19, by investigating a Ttc19?/? mouse model that shows progressive neurological and metabolic decline, decreased complex III activity, and increased production of reactive oxygen species. By using both the Ttc19?/? mouse model and a range of human cell lines, we demonstrate that TTC19 binds to the fully assembled complex III dimer, i.e., after the incorporation of the iron-sulfur Rieske protein (UQCRFS1). The insitu maturation ofUQCRFS1 produces N-terminal polypeptides, which remain bound to holocomplex III. We show that, in normal conditions, these UQCRFS1 fragments are rapidly removed, but when TTC19 is absent they accumulate within complex III, causing its structural and functional impairment.

Cervical pseudomeningocele-induced hydrocephalus following traumatic brachial plexus injury-–a case report

Introduction: We report a case of a 49-year-old man who sustained a left brachial plexus injury and traumatic brain injury after a motor vehicle accident and subsequently developed a giant left cervical pseudomeningocele. The patient suffered multiple fractures in the cervical and thoracic ribs, transverse processes and the scapula. Physical examination revealed a giant left supraclavicular mass restricting his ability to turn his head ipsilaterally, with head tilted to the right, consistent with complete plexus avulsion. Neurological examination showed progressive muscular atrophy and a positive Tinel’s sign and paresthesias of the left hand. Methods: MRI and CT revealed a giant cervical pseudomeningocele. Left hemilaminectomy and partial medial facetectomy were performed for an extradural repair of the cyst. Three days later, the pseudomeningocele recurred; C6-T2 cervical laminectomy and a combined intra- and extradural repair of CSF leak with tensor fascia lata graft were performed. One day after the second surgery, the patient developed acute communicating hydrocephalus (CH) with progressive neurological decline. Results: Ventriculoperitoneal shunt placement successfully resolved neurological symptoms associated with CH. The patient continued receiving treatment for neuropathic pain and spams in the left upper arm at one-year follow up. Conclusion: We present one of the few documented cases of acute CH after a successful repair of a giant cervical pseudomeningocele. It is important for physicians to be aware of changes in CSF flow dynamics that occur in patients with traumatic brain injury. A repair of a large chronic pseudomeningocele can lead to acute CH in patients and cause rapid neurological decline. It is critical for clinicians to be mindful of the potential complication of acute hydrocephalus in patients who undergo repair of a large chronic pseudomeningocele secondary to trauma.

Late Presentation of Fatal Hyperammonemic Encephalopathy After Roux-En-Y Gastric Bypass

Worldwide, there have been <25 reported cases of hyperammonemic encephalopathy associated with Roux-en-Y gastric bypass surgery in the absence of cirrhosis. We describe a 42-year-old woman who presented with subacute but progressive neurological decline late in her postoperative course, which deteriorated despite multiple conservative and aggressive measures, including hemodialysis, in an attempt to reduce measured plasma ammonia levels. This syndrome of hyperammonemic encephalopathy represents a serious, underrecognized, and potentially treatable complication after Roux-en-Y gastric bypass.

Management of degenerative cervical myelopathy - An update.

Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction in adult patients. Patients generally present with a slow, progressive neurological decline or a stepwise deterioration pattern. In this paper, we discuss the most important factors involved in the management of DCM, including a discussion about the surgical approaches. The authors performed an extensive review of the peer-reviewed literature addressing the aforementioned objectives. Although the diagnosis is clinical, magnetic resonance imaging (MRI) is the study of choice to confirm stenosis and also to exclude the differential diagnosis. The severity the clinical symptoms of DCM are evaluated by different scales, but the modified Japanese Orthopedic Association (mJOA) and the Nürick scale are probably the most commonly used. Spontaneous clinical improvement is rare and surgery is the main treatment form in an attempt to prevent further neurological deterioration and, potentially, to provide some improvement in symptoms and function. Anterior, posterior or combined cervical approaches are used to decompress the spinal cord, with adjunctive fusion being commonly performed. The choice of one approach over the other depends on patient characteristics (such as number of involved levels, site of compression, cervical alignment, previous surgeries, bone quality, presence of instability, among others) as well as surgeon preference and experience. Spine surgeons must understand the advantages and disadvantages of all surgical techniques to choose the best procedure for their patients. Further comparative studies are necessary to establish the superiority of one approach over the other when multiple options are available.

Anaplastic large cell lymphoma of the spinal cord.

A 28-year-old man with a 2-months history of low back pain and 3-days history of fever. Physical examination revealed limited range of motion while bending. MRI of S-spine showed bony destruction over S1 surrounded by inflammatory process from S4-S2 with epidural invasion. The patient underwent empiric antibiotic treatment with due to suspected underlying osteomeylitis. Given the known compression on MR image ,urgent surgical decompression and fusion was elected to prevent progressive neurological decline. Histological specimen analysis was consistent with as highly aggressive anaplastic large cell lymphoma.

Cellular transplant therapies for globoid cell leukodystrophy: Preclinical and clinical observations.

Globoid cell leukodystrophy (GLD) is a progressive neurodegenerative disorder caused by the deficiency of galactocerebrosidase (GALC), resulting in accumulation of toxic metabolites in neural tissues. Clinically variable based on age of onset, infantile GLD is generally a rapidly fatal syndrome of progressive neurologic and cognitive decline, whereas later-onset GLD has a more indolent, protracted clinical course. Animal models, particularly the twitcher mouse, have allowed investigation of both the pathophysiology of and the potential treatment modalities for GLD. Cellular therapy for GLD, notably hematopoietic cell transplantation (HCT; transplantation of bone marrow, peripheral blood stem cells, or umbilical cord blood cells) from a normal related or unrelated allogeneic donor provides a self-renewing source of GALC in donor-derived cells. The only currently available treatment option in human GLD, allogeneic HCT, can slow the progression of the disease and improve survival, especially when performed in presymptomatic infants. Because persistent neurologic dysfunction still occurs after HCT in GLD, preclinical studies are evaluating combinations of HCT with other treatment modalities. © 2016 Wiley Periodicals, Inc.

Intramedullary cavernoma: A surgical resection technique

Intramedullary spinal cavernoma is a rare vascular disease constituting 5–12% of all spinal vascular tumors. The clinical course is usually characterized either by an acute neurological deterioration, recurrent episodes of neurological deficits or by a slowly progressive neurological decline. Microsurgical removal is recommended when the symptoms become clinically relevant and the lesion appears accessible. In this article, we present a surgical technique to completely resect an intramedullary cavernoma with the aid of intraoperative electrophysiological monitoring and intraoperative real-time ultrasound guidance. A brief description of current management of this pathology is also presented.

Creating a caregiver program in neuro-oncology.

Neuro-oncology caregivers face unique challenges. Caring for a patient who has a catastrophic, life-threatening diagnosis combined with progressive neurological decline can produce great distress. Experts agree that a formalized plan of care to address the needs of the neuro-oncology caregiver is needed. In 2013, the Division of Neuro-Oncology at the University of California, San Francisco initiated a program designed to provide additional services to address the needs of the neuro-oncology caregiver. Records have been kept outlining program development, the caregivers seen, their identified needs, and services provided. From October 2013 through August 2015 staff met with 334 "new to clinic" caregivers, 90 of whom were caring for patients with newly diagnosed glioblastoma. One hundred ninety-eight caregivers were deemed at high risk for distress due to transitions in patient care that were occurring. One hundred forty-nine caregivers of former patients received bereavement services for up to 6 months. The areas of highest need were emotional support and advocacy issues. The number of caregiver needs increased as patients moved along the disease trajectory. The program was able to identify resources that were lacking. Dedicated staff allowed for improvement in the kinds of caregiver-specific support services offered. Dedicated caregiver staff allows for developing relationships with caregivers across the disease trajectory and appears to be important in being able to offer individualized assessments and tailored care plans. Evaluation of caregiver and patient outcomes is the next step in understanding program effectiveness.