Progressive Neurological Signs Research Articles

Gemistocytic astrocytoma in the spinal cord in a dog: a case report

ABSTRACT This paper reports a case of a rare variant of the cervical spinal cord astrocytoma diagnosed in a dog with progressive neurological signs, initially asymmetrical, not ambulatory tetraparesis, segmental reflexes and normal muscle tone in all four limbs and absence of pain upon palpation of the cervical spine. Myelography revealed attenuation of the ventral and dorsal contrast line in the third region of the fifth cervical vertebra. At necropsy intramedullary cylindrical mass that stretched from the third to the sixth cervical vertebra, which replaced all the gray matter of the spinal cord was observed. In the histological study, there was the replacement of the substance by neoplastic cells mantle arranged loosely. The cells were large and slightly rounded. The eosinophilic cytoplasm was well defined, sometimes forming processes interconnecting cells. The nucleus was eccentric, round, oval or kidney-shaped, and the nucleolus was evident. Thus, the microscopic changes observed in the cervical spinal cord were consistent with gemistocytic astrocytoma.

Startle Response in Progressive Myoclonic Epilepsy.

Cortical reflex myoclonus is a typical feature of progressive myoclonic epilepsy (PME) in which it is accompanied by other types of mostly drug-resistant seizures and progressive neurological signs. Although PME is characterized by cortical hyperexcitability, studies have demonstrated atrophy and degenerative changes in the brainstem in various types of PME. Thus, we have questioned whether any stimuli may trigger a hyperactive response of brainstem reticular formation in PME and investigated the startle reflex in individuals with PME. We recorded the auditory startle response (ASR) and the startle response to somatosensory inputs (SSS) in patients with PME, and compared the results with healthy volunteers and patients with other types of drug-resistant epilepsy. All patients were using antiepileptic drugs (AEDs), 12 were on multiple AEDs. The probability of ASR was significantly lower and mean onset latency was longer in patients with PME compared with other groups. SSS responses over all muscles were low in both the PME and drug-resistant epilepsy groups; however, the differences were not statistically significant. The presence of a response over the biceps brachii muscle was zero in the PME group and showed a borderline difference compared with the other groups. Decreased probability and prolonged latencies of ASR in PME indicate inhibition of reflex circuit. A trend for decreased responses of SSS suggests hypoactive SSS in both PME and other epilepsy groups. Hypoactive ASR in PME and hypoactive SSS in both PME and other epilepsies may be attributed to the degeneration of pontine reticular nuclei in PME and functional inhibition by AEDs in both disorders.

P.006 Keeping neurosarcoidosis on the differential

Background: Sarcoidosis is a multiorgan autoimmune disease characterized by the presence of non-caseating granulomas. The diagnosis can be difficult, particularly with central nervous system (CNS) involvement, and pathology outside of the CNS has to be carefully evaluated. Early and correct diagnosis is crucial for appropriate management particularly in children where sarcoidosis and neurosarcoidosis are rare. Methods: We describe a 16 year old previously healthy boy who presented with progressive pyramidal neurological signs and symptoms localizable primarily to the brain stem. Results: Initial imaging revealed striking brainstem, as well as cerebral, cerebellar and spinal cord perivascular enhancement. Lung involvement was subclinical with a miliary pattern on chest imaging and needle biopsy revealed an interstitial lymphocytic infiltration. Extensive serum and CSF rheumatological, autoimmune and infectious investigations were noncontributory. Serum ACE levels were at first within normal limits. Steroid treatment stabilized symptoms and perhaps coincidentally, separate rituximab treatments were followed within days by vertigo (with a new pontine lesion) or a respiratory decompensation. A wedge lung biopsy revealed granulomatosis. Current treatment consists of mycophenolate, methotrexate with a prednisone wean. Conclusions: This case report reinforces the varied manifestations and mimics of sarcoidosis (including CLIPPERS) and highlights the need for a high index of suspicion despite apparently negative investigations.

Repeated Imaging for Diagnosis of Low Back Pain

Diagnostic imaging is indicated for patients with low back pain only if they have severe progressive neurologic deficits or signs or symptoms that suggest a serious or specific underlying condition. In other patients, evidence indicates that routine imaging is not associated with clinically meaningful benefits but can lead to harm. Addressing inefficiencies in diagnostic testing could minimize potential harm to patients and have a large effect on the use of resources by reducing both direct and downstream costs.

Neuronal ceroid lipofuscinosis associated with an MFSD8 mutation in Chihuahuas.

The neuronal ceroid lipofuscinoses (NCLs) are hereditary neurodegenerative disorders characterized by progressive declines in neurological functions, seizures, and premature death. NCLs result from mutations in at least 13 different genes. Canine versions of the NCLs can serve as important models in developing effective therapeutic interventions for these diseases. NCLs have been described in a number of dog breeds, including Chihuahuas. Studies were undertaken to further characterize the pathology of Chihuahua NCL and to verify its molecular genetic basis. Four unrelated client owned Chihuahuas from Japan, Italy and England that exhibited progressive neurological signs consistent with a diagnosis of NCL underwent neurological examinations. Brain and in some cases also retinal and heart tissues were examined postmortem for the presence of lysosomal storage bodies characteristic of NCL. The affected dogs exhibited massive accumulation of autofluorescent lysosomal storage bodies in the brain, retina and heart accompanied by brain atrophy and retinal degeneration. The dogs were screened for known canine NCL mutations previously reported in a variety of dog breeds. All 4 dogs were homozygous for the MFSD8 single base pair deletion (MFSD8:c.843delT) previously associated with NCL in a Chinese Crested dog and in 2 affected littermate Chihuahuas from Scotland. The dogs were all homozygous for the normal alleles at the other genetic loci known to cause different forms of canine NCL. The MFSD8:c.843delT mutation was not present in 57 Chihuahuas that were either clinically normal or suffered from unrelated diseases or in 1761 unaffected dogs representing 186 other breeds. Based on these data it is almost certain that the MFSD8:c.843delT mutation is the cause of NCL in Chihuahuas. Because the disorder occurred in widely separated geographic locations or in unrelated dogs from the same country, it is likely that the mutant allele is widespread among Chihuahuas. Genetic testing for this mutation in other Chihuahuas is therefore likely to identify intact dogs with the mutant allele that could be used to establish a research colony that could be used to test potential therapeutic interventions for the corresponding human disease.

Clinical and Genetic Characterization of 26 Tunisian Patients with Allgrove Syndrome

Allgrove syndrome is characterized by achalasia, alacrima, and adrenal insufficiency as well as being associated with progressive neurological signs. This is an autosomal recessive disorder due to mutations in the AAAS gene located on chromosome 12q13. The AAAS gene encodes a protein of 546 amino acids, ALADIN. Mutations in this genwere reported in families from North Africa and Europe. Our objective is to conduct a clinical, molecular and genetic study of 26 Tunisian patients with Allgrove syndrome. We report 26 Tunisian patients with between two and four clinical features associated with Allgrove syndrome. Blood samples were collected and isolated DNA derived from subjects was amplified. The entire sequence of the AAAS gene was analyzed by PCR and sequencing. PCR-RFLP method was performed to identify the frequent mutations found. Sequencing of the AAAS gene revealed a major homozygous mutation (c.1331+1G>A) in 25 patients and R286X mutation in one patient. The presence of a major mutation in several unrelated affected individuals suggests the presence of a founder effect in Tunisia and allows for a fast and targeted molecular diagnosis. We created an easy and rapid molecular enzymatic protocol based on PCR-RFLP using MvaI restriction enzyme that directly targets this major mutation and can be used for prenatal diagnosis and genetic counseling for Tunisian families at risk. To the best of our knowledge, this is the first major series report of Allgrove syndrome in Tunisia.

Subacute Intracranial Subdural Hematoma 40 Days After Spinal Anesthesia: A Case Report

Introduction: Subdural hematoma is a serious but rare complication of spinal anesthesia. Differentiation between post-dural puncture headache (PDPH) and subdural hematoma can be difficult. Case Presentation: A 32-year-old female patient underwent elective cesarean section under spinal anesthesia. Ten days postoperatively, the patient developed symptoms of headache and nausea, which progressed over time. The patient was brought to the emergency department on the 40th postoperative day with hemiparesis on the left side of the body. Brain MRI revealed a sub acute subdural hematoma. Progressive neurologic signs and evidence of mass effect and cerebral shifting on brain imaging were clear indications for surgical intervention. The patient recovered completely after surgical decompression. Conclusions: A high index of suspicion for the pattern and characteristics of headache, and a meticulous neurologic examination, can help the emergency physician recognize the serious entity of subdural hematoma.

Systemic acanthamoebiasis associated with canine distemper in dogs in the semiarid region of Paraíba, Brazil

Infections by free-living amoebae can cause systemic disease in animals and humans. We describe the epidemiological, clinical and pathological aspects of disseminated acanthamoebiasis associated with canine distemper in three dogs of the semiarid region of Paraíba, Northeastern Brazil. Affected dogs developed progressive neurological and respiratory signs that progressed to death within in two to 20 days. Gross lesions were irregular and with yellow-reddish nodules randomly distributed in the lungs, heart, kidneys, spleen, lymph nodes, adrenals, and intestine. One dog had foci of malacia in the parietal cortex and another one in nucleus of brain basis. Histologically, pyogranulomas with areas of necrosis and hemorrhage in all organs affected were observed, associated with myriads of intralesional amoebic trophozoites. All three cases were concomitant canine distemper, that possibly triggered immunosuppression in the dogs. The diagnosis was performed through microscopic findings of infection by free-living amoebae and confirmed Acanthamoeba sp. by immunohistochemistry

Clinical, Laboratory, Diagnostic, and Histopathologic Features of Diethylene Glycol Poisoning—Panama, 2006

Diethylene glycol is a toxic industrial solvent responsible for more than 13 mass poisonings since 1937. Little is known about the clinical spectrum, progression, and neurotoxic potential of diethylene glycol-associated disease because of its high mortality and the absence of detailed information in published mass poisoning reports. This incident includes the largest proportion of cases with neurotoxic signs and symptoms. We characterize the features of a diethylene glycol mass poisoning resulting from a contaminated cough syrup distributed in Panama during2006. This was a retrospective chart review and descriptive analysis in a tertiary level, urban health care facility. Acase was a person admitted to the Social Security Metropolitan Hospital in Panama City between June 1 and October 22, 2006, with unexplained acute kidney injury and a serum creatinine level of greater than or equal to 2 mg/dL, or unexplained chronic renal failure exacerbation (>2-fold increase in baseline serum creatinine level) and history of implicated cough syrup exposure. Main outcomes and measures were demographic, clinical, laboratory, diagnostic, histopathologic, and mortality data with descriptive statistics. Forty-six patients met inclusion criteria. Twenty-four (52%) were female patients; median age was 67 years (range 25 to 91 years). Patients were admitted with acute kidney injury or a chronic renal failure exacerbation (median serum creatinine level 10.0 mg/dL) a median of 5 days after symptom onset. Forty patients (87%; 95% confidence interval [CI] 74% to 95%) had neurologic signs, including limb (n=31; 77%; 95% CI 62% to 89%) or facial motor weakness (n=27; 68%; 95% CI 51% to 81%). Electrodiagnostics in 21 patients with objective weakness demonstrated a severe sensorimotor peripheral neuropathy (n=19; 90%; 95% CI 70% to 99%). In 14 patients without initial neurologic findings, elevated cerebrospinal fluid protein concentrations without pleocytosis were observed: almost all developed overt neurologic illness (n=13; 93%; 95% CI 66% to 100%). Despite use of intensive care and hemodialysis therapies, 27 (59%) died a median of 19 days (range 2 to 50 days) after presentation. A high proportion of patients with diethylene glycol poisoning developed progressive neurologic signs and symptoms in addition to acute kidney injury. Facial or limb weakness with unexplained acute kidney injury should prompt clinicians to consider diethylene glycol poisoning. Elevated cerebrospinal fluid protein concentrations without pleocytosis among diethylene glycol-exposed persons with acute kidney injury may be a predictor for progressive neurologic illness.

Cyclic mood disorder heralding adult-onset autosomal dominant leucodystrophy: A clinical masquerader

Leucodystrophies are a heterogeneous group of progressive white matter diseases which may be inherited in dominant, recessive or X-linked fashion depending on the type. Adrenoleucodystrophy (ALD) and metachromatic leucodystrophy (MLD) are rather commoner forms of leucodystrophies whereas krabbes disease, alexander disease, cannavans disease etc. are of less common type. Adult-onset autosomal dominant leucodystrophy (ADLD) is a lately described rarer form of leucodystrophy with perhaps no case report from India. Various leucodystrophies may have different clinical presentations, ranging from subtle cognitive and psychiatric manifestations to gross motor disabilities, visual impairment and seizure. Psychiatric manifestations in the form of psychoses and frank schizophrenia are commonly described in MLD. Depression though uncommonly reported in MLD, cyclic mood disorders have been rarely described in any form of leucodystrophies. We are reporting an eye opener, a case of ADLD which masqueraded as a rapid cyclic mood disorder for initial four years, later to be followed by progressive neurological signs and symptoms. To the best of our knowledge, this is perhaps the first case report of ADLD presenting as rapid cyclic mood disorder in the world literature.

Noncontiguous lumbar vertebral hemangiomas treated by posterior decompression, intraoperative kyphoplasty, and segmental fixation

Vertebral hemangiomas are benign lesions and are often asymptomatic. Most vertebral hemangiomas that cause cord compression and neurological symptoms are located in the thoracic spine and involve a single vertebra. The authors report the rare case of lumbar hemangiomas in a 60-year-old woman presenting with severe back pain and rapidly progressive neurological signs attributable to 2 noncontiguous lesions. After embolization of the feeding arteries, no improvement was noted. Thus, the authors performed open surgery using a combination of posterior decompression, intraoperative kyphoplasty, and segmental fixation. The patient experienced relief from back and leg pain immediately after surgery. At 3 months postoperatively, her symptoms and neurological deficits had improved completely. To the authors' knowledge, this is the first description of 2 noncontiguous extensive lumbar hemangiomas presenting with neurological symptoms managed by such combined treatment. The combined management seems to be an effective method for treating symptomatic vertebral hemangiomas.

Chronic Compressive Myelopathy and Progressive Neurologic Signs Associated with Melarsomine Dihydrochloride Administration in a Dog

A 7 yr old castrated male Great Dane presented with a history of progressive myelopathy following the intramuscular injection of melarsomine dihydrochloride 8 wk previously. MRI revealed paraspinal and epidural abscesses at the 13th thoracic (T13) and first lumbar (L1) disc space. The dog's condition worsened despite medical management, necessitating surgical decompression. Surgical decompression resulted in rapid improvement of the patient's clinical signs. Histopathologic evaluation of the lesions revealed pyogranulomatous inflammation. Cultures of fluid and tissue within the lesions were negative for bacterial growth, and no infectious organisms were visualized histologically. Melarsomine-associated neurologic signs can be chronic and progressive in nature, presumably secondary to ongoing sterile inflammation that may result in spinal cord compression.

CONGENITAL GLYCOGEN STORAGE DISEASE IN A SOUTH AMERICAN COATI (NASUA NASUA)

A 14-mo-old South American coati (Nasua nasua) was submitted for necropsy to the University of Kentucky Veterinary Diagnostic Laboratory. The coati had a history of progressive neurologic signs beginning 3 mo prior to euthanasia. At necropsy, the coati was in thin body condition, but no other significant findings were evident. Histopathologic findings included moderate distension of neuronal cell bodies by finely vesiculated cytoplasm within the cerebrum, cerebellum, spinal cord, and intestinal ganglia. Hepatocytes and macrophages in the lung, spleen, and liver were similarly affected. Transmission electron microscopy showed numerous electrondense membranous cytoplasmic bodies, swirls, and vesicular profiles within neuronal lysosomes in the brain. To the authors' knowledge, this is the first report of a naturally occurring congenital glycogen storage disease in a South American coati and the family Procyonidae.

Dialysis disequilibrium syndrome occurring during continuous renal replacement therapy.

The dialysis disequilibrium syndrome (DDS) is characterized by progressive neurological symptoms and signs attributable to cerebral edema that occurs due to fluid shifts into the brain following a relatively rapid decrease in serum osmolality during hemodialysis (HD). Since continuous renal replacement therapy (CRRT) is less efficient at solute clearance than intermittent HD, it seems logical that this mode of therapy is less likely to cause DDS. This entity has not been previously reported to occur with this modality. Here, we report two cases of DDS associated with CRRT that provide insights into its pathophysiological mechanisms and suggest strategies for its prevention.

Phase II trial of carboplatin (C) and bevacizumab (BEV) in patients (pts) with breast cancer brain metastases (BCBM).

513 Background: The anti-tumor and anti-edema effects of BEV provide a rationale for testing in BCBM. Carboplatin (C) is associated with CNS responses across multiple tumor types. We evaluated BEV + C in pts with BCBM. Methods: Pts with progressive, measurable BCBM (>/= 1 cm in longest dimension) were eligible. Cycle 1: BEV 15 mg/kg on Day 1, followed on Day 8 by carboplatin AUC=5 (plus trastuzumab if HER2+). In subsequent cycles, pts received BEV + C on Day 1 (plus trastuzumab if HER2+) of a 3 week (wk) cycle. Standard brain MRI was obtained at baseline (BL) and every 2 cycles. Non-CNS scans (CT or MRI) were performed after 2 cycles, 4 cycles, then every 4 cycles. Correlative brain imaging was obtained at BL, 12-96 hours after the first dose of BEV, and after 2 cycles. Circulating tumor cells and blood for VEGF polymorphisms were also collected. The primary endpoint was composite CNS objective response rate (CNS ORR). CNS partial response required all of the following: >/= 50% reduction in volumetric sum of target CNS lesions compared to BL, no progression of non-target lesions, no new lesions, stable/decreasing steroid dose, no progressive neurologic signs or symptoms, and no progression of non-CNS disease by RECIST 1.0. The study used a 2-stage design to distinguish between ORR 5% vs 20% (responses in >/= 1/12 pts to enter 2ndstage; responses in >/= 4/37 pts needed to be promising). Results: 38 pts were enrolled between 11/3/09-8/24/12 (30 HER2+; 8 HER2-negative). Most (76%) pts had received >/=2 lines of metastatic chemotherapy. 97% of pts with HER2+ disease received prior trastuzumab; 73% had prior lapatinib. All but 5 pts progressed after WBRT and/or SRS. As of 1/15/13, 3 pts remain on protocol therapy; 22 patients have died. The composite CNS ORR was 63% (95% CI 46%-78%). CNS ORR by RECIST was 45%. CNS responses were observed in both HER2+ and HER2-negative pts. Of 34 pts with >/= 24 wks potential follow-up time, median number of cycles was 8 (range 1-19). One grade 2 CNS hemorrhage event was reported; there were no cases of grade 3/4 CNS hemorrhage. Conclusions: BEV + carboplatin is associated with a high rate of durable CNS response in pts with BCBM. Updated results, including progression-free and overall survival will be presented. Clinical trial information: NCT01004172.

A case of diffuse bilateral scrotal neurofibroma in a rabbit

This report details a rare case of diffuse bilateral scrotal neurofibroma complicated by hindlimb paralysis in a rabbit. The animal was evaluated for unusual bilateral scrotal enlargement. After physical examination, ultrasound scan, radiography, computed tomography and laparoscopy, surgical exploration of the scrotum was undertaken. A homogeneous rubbery firm mass was revealed in contact with the subcutaneous tissue expanding to the entire scrotum without involving the testicles. The mass was excised and diagnosed as diffuse scrotal neurofibroma based on histological and immunohistochemical findings (S-100 antibody positive). Over the following month, progressive neurological signs (faecal incontinence, flaccid bladder and hindlimb paralysis) were observed. After excluding central nervous system infection with Encephalitozoon cuniculi, expansion of the neurofibroma to the vertebral canal causing compression of the spinal cord was suspected, although not histopathologically verified.

Clinical conundrum

A 4-year-old Hungarian Vizsla presented with a 7 day history of progressive neurological signs including stumbling and bumping into objects. Diagnosis and treatment of a meningoencephalitis are described.

Algal Meningoencephalitis due toProtothecaspp. in a Dog

A 6-year-old Boxer was examined because of progressive neurologic signs, with severe hindlimb ataxia and head tilt on presentation. There was no history of diarrhea or vomiting. MRI of the brain revealed multifocal ill-defined T1-enhancing lesions affecting the cerebrum, brainstem, and cervical meninges, without associated mass effect. Meningoencephalitis was considered the most likely diagnosis. Multiple algae were observed on the cytology of the CSF and were most consistent withProtothecaspp. Antiprotozoal treatment was denied by the owners, and 5 weeks after diagnosis, the dog was euthanized due to progression of the neurologic deficits, and a necropsy was performed. Histological changes in the brain were compatible with severe multifocal protothecal meningoencephalitis. The specificProtothecaspecies was not identified. The gastrointestinal tract was unremarkable on histology. According to this report,Protothecaspp. should be included in the differentials for neurological deficits even in the absence of gastrointestinal signs.

Severe Subacute Necrotizing Encephalopathy (Leigh-like Syndrome) in American Staffordshire Bull Terrier Dogs

Seventeen American Staffordshire bull terrier puppies, 6-8 weeks of age, from seven closely related litters, presented with rapidly progressive central vestibular neurological signs. Previously reported hereditary ataxias in the breed, including l-2 hydroxyglutaric aciduria and cerebellar cortical degeneration, as well as thiamine deficiency, were excluded. Elevated lactate levels and lactate:pyruvate ratios gave supporting evidence of a defect of the respiratory chain or Leigh-like syndrome. Histopathology in all cases showed a bilaterally symmetrical necrotizing encephalopathy, with malacia of the neuropil centred on the vestibular and olivary nuclei of the brainstem. This is the first documentation of a heritable rapidly progressive lethal necrotizing encephalopathy consistent with Leigh-like syndrome, in American Staffordshire bull terrier dogs.

A Rare Variant of Multicentric Large B-cell Lymphoma with Plasmacytoid and Mott Cell Differentiation in a Dog

This report details the diagnosis and immunohistochemical characterisation of a disseminated B-cell lymphoma with a predominant Mott cell phenotype in a 5-year-old, neutered male Australian shepherd dog. The dog presented with progressive neurological signs as a result of cerebrocortical involvement.