Clinical Neurological Signs Research Articles

Outcome prediction by motor and pupillary responses in children treated with therapeutic hypothermia after cardiac arrest*

Clinical neurologic signs considered predictive of adverse outcome after pediatric cardiac arrest may have a different prognostic value in the setting of therapeutic hypothermia. We aimed to determine the prognostic value of motor and pupillary responses in children treated with therapeutic hypothermia after cardiac arrest. Prospective cohort study. Pediatric intensive care unit in tertiary care hospital. Children treated with therapeutic hypothermia after cardiac arrest. Thirty-five children treated with therapeutic hypothermia after cardiac arrest were prospectively enrolled. Examinations were performed by emergency medicine physicians and intensive care unit bedside nurses. Examinations were performed after resuscitation, 1 hr after achievement of hypothermia, during the last hour of hypothermia, 1 hr after achievement of normothermia, after 24 hrs of normothermia, and after 72 hrs of normothermia. The primary outcome was unfavorable outcome at intensive care unit discharge, defined as a pediatric cerebral performance category score of 4-6 at hospital discharge. The secondary outcome was death (pediatric cerebral performance category = 6). The associations between exam responses and unfavorable outcomes (as both pediatric cerebral performance category 4, 5, 6 and pediatric cerebral performance category 6) are presented as positive predictive values, for both all subjects and subjects not receiving paralytics. Statistical significance for these comparisons was determined using Fisher's exact test. At all examination times and examination categories, positive predictive values were higher for the unfavorable outcome pediatric cerebral performance category 4, 5, 6 than the pediatric cerebral performance category 6. By normothermia hour 24, absent motor and pupil responses were highly predictive of unfavorable outcome (pediatric cerebral performance category 4, 5, 6) (positive predictive value 100% and p < .03 for all categories), while at earlier times the predictive value was lower. Absent motor and pupil responses are more predictive of unfavorable outcome when defined more broadly than when defined as only death. Absent motor and pupil responses during hypothermia and soon after return of spontaneous circulation were not predictive of unfavorable outcome while absent motor and pupil responses once normothermic were predictive of unfavorable short-term outcome. Further study is needed using more robust short-term and long-term outcome measures.

Vitamin B12 and Homocysteine Levels and 6-Year Change in Peripheral Nerve Function and Neurological Signs

Low vitamin B12 and high homocysteine (Hcy) levels are common in older adults and may be associated with worse neurological function. The aim of this study is to determine whether changes in B12 or Hcy levels are associated with longitudinal changes in peripheral nerve function and clinical neurological signs and symptoms. Participants aged 60 years and older at baseline (n = 678; 72.2 ± 6.2 years; 43.5% male) were from the InCHIANTI Study. Low B12 (<260 pmol/L) and high Hcy (≥13 μmol/L) were measured at baseline and 3-year follow-up. Neurological function was assessed by peroneal nerve conduction amplitude (compound motor action potential) and velocity, neurological examination, and peripheral neuropathy symptoms at baseline, 3-year, and 6-year follow-up. At baseline, 43.8% had low B12 levels and 58.6% had high Hcy levels. Over 6 years, 12.4% declined to poor compound motor action potential (<1 mV) and 42.1% declined to poor nerve conduction velocity (<40 m/s). In mixed models analyses, sustained high Hcy was associated with worse compound motor action potential compared with sustained normal Hcy (p = .04), adjusting for demographics, diabetes, and folate level. Participants whose Hcy level became high at follow-up were more likely to become unable to detect monofilament at 6-year follow-up compared with those with sustained normal Hcy (odds ratio: 5.4; 95% CI: 1.5-19.0), adjusting for demographics, diabetes, body mass index, and peripheral arterial disease. There was no association with vitamin B12 level or with symptoms. High Hcy may be associated with worse sensory and motor peripheral nerve function. Because poor nerve function has been associated with lower strength and physical performance, these results have important implications for disability in older adults.

Can cerebral microbleeds cause an acute stroke syndrome?

GRE T2* MRI sequences are sensitive to tiny areas of previous bleeding (termed cerebral microbleeds [CMBs])1 due to the paramagnetic effects of blood degradation products including oxyhemoglobin and hemosiderin. CMBs are common and may be a prognostic marker of recurrent intracerebral hemorrhage,2 including antithrombotic related hemorrhage.3 Studies suggest that the chronic accumulation of CMBs may have an effect on anatomically distributed cerebral functions including cognition.4 As microbleeds cause focal damage to the brain tissue,5 acutely developing microbleeds might be expected to cause focal symptoms. We report 2 cases of acute focal neurologic symptoms and clinical signs that in each case appeared to be due to a CMB. ### Case 1 A 69-year-old right-handed man with known hypertension awoke feeling dizzy and unsteady (“as if the room was spinning around him”) and had numbness around his mouth and on his right cheek. When examined 2.5 hours later, his systolic blood pressure was >200 mm Hg and he had a right VII lower motor neuron palsy, gait ataxia, and gaze-evoked nystagmus on right gaze. An urgent CT head and CT angiogram showed no focal abnormality (figure e-1). MRI using a Siemens 1.5 Tesla scanner was performed on the same day. GRE T2*-weighted sequences showed a CMB centered …

Predictive value of neurological examination for early cortical responses to somatosensory evoked potentials in patients with postanoxic coma

Bilateral absence of cortical N20 responses of median nerve somatosensory evoked potentials (SEP) predicts poor neurological outcome in postanoxic coma after cardiopulmonary resuscitation (CPR). Although SEP is easy to perform and available in most hospitals, it is worthwhile to know how neurological signs are associated with SEP results. The aim of this study was to investigate whether specific clinical neurological signs are associated with either an absent or a present median nerve SEP in patients after CPR. Data from the previously published multicenter prospective cohort study PROPAC (prognosis in postanoxic coma, 2000–2003) were used. Neurological examination, consisting of Glasgow Coma Score (GCS) and brain stem reflexes, and SEP were performed 24, 48, and 72 h after CPR. Positive predictive values for predicting absent and present SEP, as well as diagnostic accuracy were calculated. Data of 407 patients were included. Of the 781 SEPs performed, N20 s were present in 401, bilaterally absent in 299, and 81 SEPs were technically undeterminable. The highest positive predictive values (0.63–0.91) for an absent SEP were found for absent pupillary light responses. The highest positive predictive values (0.71–0.83) for a present SEP were found for motor scores of withdrawal to painful stimuli or better. Multivariate analyses showed a fair diagnostic accuracy (0.78) for neurological examination in predicting an absent or present SEP at 48 or 72 h after CPR. This study shows that neurological examination cannot reliably predict absent or present cortical N20 responses in median nerve SEPs in patients after CPR.

Granulomatous Meningoencephalitis Due to Toxoplasma gondii in a Black-headed Night Monkey (Aotus nigriceps)

This report describes toxoplasmosis infection in a black-headed night monkey (Aotus nigriceps) from the Zoological Park of the Federal University of Mato Grosso, Brazil. The animal was submitted alive to the Veterinary Hospital of the Federal University of Mato Grosso presenting neurologic clinical signs. There were no improvements on the animal's clinical condition after treatment, so it was euthanized. At necropsy, the most significant gross lesions observed were hemorrhages diffusely scattered throughout the cerebral hemispheres. Histologic findings were characterized by nonsuppurative encephalitis and mild multifocal necrotizing nonsuppurative myocarditis. Groups of tachyzoites and cysts were observed surrounding the inflamed areas of cerebral parenchyma. Sections of the brain were submitted for immunohistochemistry examination for Toxoplasma gondii and Neospora caninum and also for polymerase chain reaction (PCR) to determine the presence of Toxoplasma gondii. The samples were positive for Toxoplasma gondii by PCR; however, cross reactivity was observed between Toxoplasma gondii and Neospora caninum antibodies. These findings were consistent with a toxoplasmosis infection in this animal.

Encephalitis and Neuronal Necrosis in a 3-Month-Old Suckled Beef Calf

A 3-month-old suckled beef calf from the west coast of Scotland showed neurologic clinical signs for 1 week and was euthanized after failing to respond to treatment. Blood and tissue samples, including the brain, were submitted for diagnosis. Histologic examination of the brain showed neuronal chromatolysis and necrosis in the hind brain and loss of Purkinje cells in the cerebellum, accompanied by mild nonsuppurative encephalitis in the hind brain with a striking lack of inflammation in the cerebellar layers. Other microscopic lesions present were mild nonsuppurative meningitis with perivascular cuffs, diffuse hypergliosis, and occasional foci of neuronophagia. Polymerase chain reaction amplification of viral nucleic acids and specific immunohistochemical labeling allowed the identification of louping ill virus, and serology showed high titers of immunoglobulin M, indicating a recent infection.

Acetylcholinesterase activity and lipid peroxidation in the brain and spinal cord of rats infected with Trypanosoma evansi

Neurological and locomotor clinical signs are described in animals infected with Trypanosoma evansi. These disturbances may be related to changes in the amount of acetylcholine (neurotransmitter) in the synaptic cleft. Therefore, changes in acetylcholinesterase (AChE) activity and lipid peroxidation in brain and spinal cord of T. evansi-infected rats were investigated. Each rat was intraperitoneally infected with 106 trypomastigotes kept in fresh (group A; n=13) and cryopreserved blood (group B; n=13). Thirteen served as uninfected (not-infected; group C). In days 4 and 30 post-infection (PI) the rats were anesthetized and subsequently decapitated to obtain the brain and the spinal cord (between vertebrae L1 and S2). The brain was removed and dissected (cerebellum, cerebral cortex, striatum and hippocampus) to measure the activity of AChE and lipid peroxidation, determined by TBARS levels. To verify if T. evansi was present in the central nervous system (CNS), brain structures of three rats of each group were processed by PCR T. evansi-specific. AChE activity was significantly increased in all brain structures and decrease in spinal cord in infected rats in 4 PI (P<0.05). The levels of TBARS were decreased in the brain structures, differently from spinal cord, which showed increased lipid peroxidation in 4 PI. The AChE activity in striatum, cerebral cortex, hippocampus and spinal cord reduced concomitantly with the increase of the enzyme in cerebellum of the infected rats (P<0.05), and the TBARS levels increased in cerebellum, striatum and spinal cord of infected rats compared to non-infected animals in 30 PI. The PCR was positive for T. evansi in all structures of the brain, confirming the presence of the parasite in the CNS. Based on the results, we conclude that the changes in AChE activity and lipid peroxidation in the CNS are induced by infection with T. evansi, suggesting that the parasite interferes with the cholinergic neurotransmission in this experimental condition.

Interconnection between biological abnormalities in borderline personality disorder: Use of the Bayesian networks model

There is agreement in that strengthening the sets of neurobiological data would reinforce the diagnostic objectivity of many psychiatric entities. This article attempts to use this approach in borderline personality disorder (BPD). Assuming that most of the biological findings in BPD reflect common underlying pathophysiological processes we hypothesized that most of the data involved in the findings would be statistically interconnected and interdependent, indicating biological consistency for this diagnosis. Prospectively obtained data on scalp and sleep electroencephalography (EEG), clinical neurologic soft signs, the dexamethasone suppression and thyrotropin-releasing hormone stimulation tests of 20 consecutive BPD patients were used to generate a Bayesian network model, an artificial intelligence paradigm that visually illustrates eventual associations (or inter-dependencies) between otherwise seemingly unrelated variables. The Bayesian network model identified relationships among most of the variables. EEG and TSH were the variables that influence most of the others, especially sleep parameters. Neurological soft signs were linked with EEG, TSH, and sleep parameters. The results suggest the possibility of using objective neurobiological variables to strengthen the validity of future diagnostic criteria and nosological characterization of BPD.

Brain tumour as a predisposing factor to head trauma: a review of two cases diagnosed by computed tomography

Brain tumours and head trauma are two pathological entities that may involve the central nervous system to produce similar clinical neurologic signs and symptoms. There has been a long-term debate in the literature on association between these two clinical conditions following observations over time of development of intracranial tumours in individuals who previously sustained head injury. In this teaching centre, there were in succession, two cases of head injury which, at brain CT scanning, turned out to be brain tumours. These findings stimulated the need to review the literature.To examine the literature for evidence of the role of brain tumour as a factor in development of falls and subsequent head injury and thus raise awareness of their association.Related literature materials on brain tumours and head injury were reviewed.Some reports in the medical literature established only weak evidence in support of head injury as an aetiologic agent for brain tumour occurrence; others found no association between them. CT and MRI are useful investigative modalities.Head trauma may only have caused small and preexisting quiescent tumour to grow as a result of predisposition to fall by musculoskeletal incoordination caused by the tumour itself.

Subclinical Venous Sinus Thrombosis Secondary to Hypernatraemic Dehydration

An 8-day-old infant was admitted to a paediatric intensive care unit with severe hypernatraemic dehydration. An MRI brain was performed which revealed extensive venous sinus thromboses. This is a recognised but rare complication of hypernatraemic dehydration and the importance of early detection and intervention of this condition is again highlighted.This is the first case report of venous sinus thrombosis secondary to hypernatraemic dehydration in a patient with no clinical neurological signs. We postulate that there may be a cohort of infants with subclinical cerebral venous thrombosis secondary to hypernatraemic dehydration.

Movement, dive behavior, and survival of California sea lions (Zalophus californianus) posttreatment for domoic acid toxicosis

Domoic acid (DA) is a neuroexcitatory toxin increasingly causing strandings and mortality of marine mammals. The hippocampus of mammalian brains, associated with learning, memory, and spatial navigation, is one of the predominant regions affected by DA exposure. California sea lions stranding from 2003 to 2006 as a result of DA toxicosis were classified as having acute (n= 12) or chronic neurologic (n= 22) clinical signs. Chronic neurologic cases were examined by magnetic resonance imaging to determine the extent of brain damage related to DA exposure. Brain damage included hippocampal and parahippocampal atrophy, temporal horn enlargement, and pathological T2 hyperintensity. Posttreatment, animals were fitted with satellite transmitters and their movement and dive behaviors compared with those of a control group. The only significant difference between acute and chronic animals was distance traveled per day. There were, however, significant differences between chronic neurologic cases and controls: chronic neurologic cases dove shallower for shorter durations, traveled further from shore, and spent less time hauled out and more time surface swimming than control animals. There was no relationship between severity of brain damage and behavioral patterns for chronic neurologic cases. Sea lions with chronic neurologic changes had a poor prognosis for survival following release.

Canine Distemper Infection in Crab-eating Fox (Cerdocyon thous) from Argentina

Canine distemper virus (CDV) has been reported worldwide in wild carnivores and has been cited as the cause of population declines in some species. Crab-eating foxes (Cerdocyon thous) from El Palmar National Park, Argentina, were observed either dead or exhibiting clinical neurologic signs. Samples were taken from two individuals that were laterfound tobe positive for CDV by direct immunofluorescence in brain tissue. Based on molecular studies, the CDV strain had a high percentage of identity compared to CDV strains affecting dogsin Argentina. This is the first report of CDV infection in wild carnivores in Argentina.

Histopathological and clinical investigations in Neospora caninum experimentally infected broiler chicken embryonated eggs

To date, despite the limited information about the role of birds in Neospora caninum infection, there are no reports regarding the role of broiler chickens. In the present study, an experimental infection with N. caninum NC-1 isolate was conducted in embryonated eggs from 70 Lohman broiler chickens randomly divided into seven equal groups. At 8 days of incubation, six groups were inoculated via chorioallantoic (CA) liquid with different dilutions (10, 10 2, 10 3, 10 4, 10 5, and 10 6) of tachyzoites/embryonated egg. The 7th group was considered the control. The mortality rate, gross and histopathologic changes of tissues of the dead embryos and live hatched chickens up to 60 days old were studied and evaluated. There were no hatchings in groups with 10 5 and 10 6 tachyzoites. In groups with 10, 10 2, 10 3 and 10 4 tachyzoites there were 8, 7, 5 and 2 hatchings, respectively. From the surviving chickens only one 10 4 tachyzoites inoculated chicken showed clinical neurologic signs. In all groups the main gross lesions were hemorrhage associated with thickening of the CA membranes. Three chickens (one chicken with 10 4 tachyzoites and two with 10 5 tachyzoites) showed arthritis in the feet joints after two weeks of inoculation. Microscopic examination of the heart, liver and chorioallantoic membrane revealed acute neosporosis and, in some cases, granulomatous inflammation. Our findings implied that broiler chicken embryonated egg is a completely suitable animal model for biological studies of acute neosporosis studies and genetic susceptibility can be propounded in different chicken breeds. It seems 10 3 tachyzoites dilution is equal to LD50 in N. caninum infection in broiler chicken embryonated eggs and can be used in other experimental investigations.

Predicting acute ischemic stroke by measuring the degree of ocular gaze deviation (Prévost's sign) on CT

Background and aimOcular gaze deviation (OGD) is a well known clinical observation (Prevost's sign) in patients with acute cerebral ischemic stroke. Although OGD has been observed on CT in acute...

Morphologic Evidence Suggestive of Hypertension in Western Gray Kangaroos (Macropus fuliginosus)

Marked renal vascular changes, suggestive of hypertension, were present in adult western gray kangaroos (Macropus fuliginosus) from a single facility over a 14-year period. A subset of these kangaroos also had vague clinical nervous system deficits, including blindness. To characterize the vascular lesions, determine prevalence, and document other changes, case histories and archival tissue sections from 21 adult kangaroos (8 male, 13 female) that died or were euthanatized between 1994 and 2008 were reviewed. Relevant lesions included increased thickness of the renal arteriolar tunica media with smooth muscle hypertrophy and/or hyperplasia, accumulation of extracellular matrix within arterioles, increased vascular tortuosity, and varying degrees of juxtaglomerular hyperplasia. Renal tissue from two more severely affected animals was further examined by transmission electron microscopy, highlighting arteriolar endothelial cell hypertrophy and disruption of the medial architecture. Hypertrophy of arteries and arterioles in other organ systems was also present (3/21), including vessels in the brain and spinal cord of one animal with clinical neurologic signs. Four kangaroos had antemortem retinal detachment, a potential sequel of hypertension in humans and domestic mammals. The cause of these vascular lesions in this mob is uncertain. Lesions were not associated with an infectious disease process, age, underlying renal disease, or thyroid abnormalities. In the absence of other causes, hypertension was a differential. Further investigation into clinical significance and predisposing factors, such as genetics and diet, is warranted.

Alpha-mannosidase activity in goats fed with Sida carpinifolia

Human α-mannosidosis results from α-mannosidase deficiency and progressive accumulation of mannose-rich oligosaccharides in lysosomes. Two days before Saanen goats were fed with Sida carpinifolia, α-mannosidase activity in leukocytes was 128±28 nmoles 4-MU/h/mg protein (first trial) and 104±6 nmoles 4-MU/h/mg protein (second trial). At day 5, after the introduction of S. carpinifolia diet, the α-mannosidase activity in leukocytes was significantly increased, both in the first (288±13 nmoles 4-MU/h/mg protein) and in the second trial (303±45 nmoles 4-MU/h/mg protein), and it returned to normal levels 2 days after the withdrawal of the plant from the diet (114±7 nmoles 4-MU/h/mg protein in first trial, and 108±25 nmoles 4-MU/h/mg protein in the second one). Plasma α-mannosidase activity decreased significantly 4 days after animal exposure to the S. carpinifolia diet (769±167 nmoles 4-MU/h/ml) and returned to normal values 10 days after the withdrawal of the plant from the diet (1289±163 nmoles 4-MU/h/ml). Thin-layer chromatography showed an abnormal excretion of oligosaccharides in urine as of day 2 after diet exposure, which persisted until one day after the withdrawal of the plant. Animals presented neurological clinical signs beginning at day 37 (in the first trial) and at day 25 (in the second trial) after being fed with the plant. The results obtained herein suggest that oligosaccharides observed in urine are a result of a decrease in α-mannosidase activity in plasma. S. carpinifolia seems to have other compounds that act on α-mannosidase enzyme in leukocytes in a competitive manner with swainsonine. The increase in α-mannosidase enzyme in leukocytes could be attributed to one of these compounds present in S. carpinifolia.

Intraoperative use of somatosensory-evoked potentials: is general anaesthesia comparable to awake condition?

Editor, We have read with great interest the article by Fielmuth and Uhlig [1] on the role of somatosensory-evoked potentials (SSEPs) in detecting cerebral ischaemia during carotid endarterectomy. The authors made an assessment of the validity of SSEP monitoring during carotid endarterectomy in awake patients under locoregional anaesthesia. They correctly reported the current substantial variety of SSEP parameters and thresholds related to these SSEP parameters used to detect critical deterioration in cerebral blood flow (CBF). Their study was designed to compare SSEP tracings with the objective clinical–neurological examination in order to evaluate the reliability of the different SSEP-generated criteria. They referred to Shapiro and Aidinis [2], who developed a model, which can be seen as the methodological basis for current neuromonitoring during carotid surgery. This model correlates neuronal integrity and electrical activity with CBF. Using this approach to interpret changes in SSEP tracing as a perfusion-dependent neuronal metabolic situation, different parameters and values have been established to detect a relevant reduction in CBF.

Neurodegenerative lysosomal storage disease in European Burmese cats with hexosaminidase β-subunit deficiency

GM2 gangliosidosis is a fatal, progressive neuronopathic lysosomal storage disease resulting from a deficiency of β- N-acetylhexosaminidase (EC 3.2.1.52) activity. GM2 gangliosidosis occurs with varying degrees of severity in humans and in a variety of animals, including cats. In the current research, European Burmese cats presented with clinical neurological signs and histopathological features typical of a lysosomal storage disease. Thin layer chromatography revealed substantial storage of GM2 ganglioside in brain tissue of affected cats, and assays with a synthetic fluorogenic substrate confirmed the absence of hexosaminidase activity. When the hexosaminidase β-subunit cDNA was sequenced from affected cats, a 91 base pair deletion constituting the entirety of exon 12 was documented. Subsequent sequencing of introns 11 and 12 revealed a 15 base pair deletion at the 3′ end of intron 11 that included the preferred splice acceptor site, generating two minor transcripts from cryptic splice acceptor sites in affected Burmese cats. In the cerebral cortex of affected cats, hexosaminidase β-subunit mRNA levels were approximately 1.5 times higher than normal ( P < 0.001), while β-subunit protein levels were substantially reduced on Western blots.

Cerebrospinal fluid cholesterols and phospholipids in phenylketonuria.

Cerebrospinal fluid (CSF) cholesterols and phospholipids were fractionated and quantitated in 64 patients with phenylketonuria (PKU). In 56 patients the results were related to clinical neurological signs and to the intellectual deficiency. PKU patients had decreased mean concentrations of esterified cholesterol, total phospholipid, sphingomyelin, and choline phosphoglyceride, and increased concentration of ethanolamine phosphoglyceride. The cholesterol but not phospholipid concentrations were significantly correlated to CSF protein concentrations. Decreased cholesterol and phospholipid concentrations were predominantly seen in patients with abnormal motor signs, and the decrease was greatest in the most affected patients. There was no relation between reduced CSF lipid concentrations and the occurrence of epilepsy or the degree of mental deficiency. The reduction of CSF cholesterol and phospholipid concentrations is probably related to myelin abnormalities, and the different results observed in relation to the neurological abnormalities and to the mental deficiency point to a difference in the pathogenesis of these disorders.

Meningitis

* Young infants who have meningitis may present with nonspecific clinical manifestations. * S. pneumoniae and N. meningitidis remain the most common causes of bacterial meningitis in the infant and child, and GBS continues to be the most common neonatal pathogen. * Empiric therapy for suspected bacterial meningitis in a non-neonate includes a combination of parenteral vancomycin and either cefotaxime or ceftriaxone. * Children whose GCS scores are less than 8, show signs of shock or respiratory compromise, and have focal neurologic findings or clinical signs of elevated intracranial pressure should be admitted to a pediatric intensive care unit. * Sensorineural hearing loss occurs in 30% of children who have pneumococcal and 10% of those who have meningococcal meningitis.