Multiple Neurological Deficits Research Articles

Progressive Multifocal Leukoencephalopathy in an Immunocompetent Taiwanese Patient

Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating brain disease caused by JC virus (JCV). Genomic analysis of viral isolates in these cases often shows prototype-like JCV and its variants, which is a virulent strain compared to the latent archetype virions mostly found in the kidney. Here, we report a 57-year-old man who suffered from a subacute course of cognitive impairment and multiple neurologic deficits. Neuroimaging, pathology, and virology studies showed multifocal leukoencephalopathy and the presence of JCV deoxyribonucleic acid in the cerebrospinal fluid. The prototype type 1 (Mad-1) strain of JCV was identified on viral genotyping obtained from brain tissue. No immune deficits were found. He responded poorly to alpha-interferon and antiviral treatment. This case suggests that lack of immune deficiency cannot exclude the possibility of PML as a cause of subacute leukoencephalopathy. Accumulated data with respect to the disease course, pathologic feature, and viral genomic subtyping may pave the way for future treatment against this devastating disease.

Fatal Systemic Phaeohyphomycosis Caused by Ochroconis gallopavum in a Dog (Canis familaris)

A 5-year-old Shetland Sheepdog was presented with a history of weakness, ataxia, anemia, thrombocytopenia, and occasional seizures. The dog had been treated for 6 months with prednisone for inflammatory bowel disease. A positive titer for Ehrlichia canis was detected 6 months before referral. The initial physical examination revealed a weak, laterally recumbent dog with pale mucous membranes. Neurologic examination revealed multiple neurologic deficits. A complete blood cell count (CBC) revealed normochromic, normocytic, nonregenerative anemia; lymphopenia; thrombocytopenia; and neutrophilic and monocytic leukocytosis. Urinalysis revealed proteinuria, with a specific gravity of 1.045. The dog was unresponsive to treatment and died. At necropsy, there was severe serofibrinous peritonitis and pleuritis, with randomly scattered dark brown necrotic foci present in multiple organs, including liver, spleen, kidney, and pancreatic lymph node. Histologically, there were extensive regions of parenchymal necrosis surrounded by neutrophils admixed with epithelioid macrophages, lymphocytes, and pigmented fungal organisms. Numerous brown, 2 to 6 microm in diameter, septate, branching hyphae, subsequently identified as Ochroconis gallopavum (formerly Dactylaria constricta var. gallopava), were observed.

Disseminated Histoplasmosis Presenting as a Unilateral Cranial Nerve VIII Mass

To report a unique presentation of disseminated histoplasmosis. Case report. University hospital, tertiary referral center. Our patient presented with vertigo, tinnitus, and unilateral hearing loss, and was initially found to have a 5-mm enhancing left internal auditory canal mass, as revealed by a magnetic resonance imaging (MRI) scan. Subsequently, the patient developed multiple focal neurologic deficits. Magnetic resonance imaging and treatment with intravenously administered amphotericin B, with subsequent oral administration of itraconazole. Clinical presentation and imaging findings of Histoplasmosis involving the cranial nerve VIII. A subsequent MRI scan revealed enlargement of the initial lesion and multiple parenchymal lesions. Further workup revealed a pulmonary lesion; the diagnosis of disseminated histoplasmosis was made on the basis of bronchoalveolar lavage culture. Infectious processes, including disseminated histoplasmosis, should be considered in the differential of internal auditory canal masses, especially in the setting of rapid progression of symptoms.

Bilirubin potentiates inhibitory synaptic transmission in lateral superior olive neurons of the rat

Bilirubin is a well-known neurotoxin that can result in multiple neurologic deficits. Previous studies have suggested that bilirubin affects aspects of synaptic transmission; however the acute effects of bilirubin on synaptic transmission have not been examined in real-time. In this study, using whole-cell voltage-clamp recordings, we observed the effect of bilirubin on inhibitory postsynaptic currents (IPSC) in postnatal 13–15-day-old neurons dissociated from lateral superior olive nuclei (LSO), one of the brainstem auditory nucleus that are highly vulnerable to bilirubin. The results showed that 10 −5 M bilirubin increased the frequency of spontaneous IPSC without causing change in their amplitudes or in the response to bath applied glycine, suggesting a presynaptic locus for the action. In the presence of tetrodotoxin, the frequency of miniature IPSC was also potentiated by 10 −5 M bilirubin. The facilitation by bilirubin was concentration dependent and increased with an increase in exposure time. Bicuculline only partially reduced the action of bilirubin. The action of bilirubin was observed in extracellular Ca 2+-free ([Ca 2+] o free) solution but was fully occluded by pretreatment with BAPTA-AM in [Ca 2+] o free solution. Thus, in LSO neurons, bilirubin facilitates inhibitory synaptic transmission, in a manner independent of voltage-activated Na + and Ca 2+ channels but dependent on presynaptic [Ca 2+] i. The increase of inhibitory synaptic transmission in response to acute bilirubin is a novel effect of bilirubin on the central nervous system and may have implications for neurotoxicity and the impairment of auditory transduction seen in hyperbilirubinemia.

REHABILITATION OF CORTICAL VISUAL IMPAIRMENT IN CHILDREN

Cortical Visual Impairment (CVI) is a condition of bilateral visual loss due to injury of visual areas in the brain without significant eye or anterior visual pathway impairment. Perinatal hypoxic ischemic encephalopathy (HIE) and postnatal anoxia are frequent etiologies of CVI and tend to result in more extensive gray and white matter injury affecting optic radiations and visual cortex. Often these children have other significant neurological disabilities and seizures as well. This article provides an analysis of a clinical database of children with CVI evaluated between January 1996 and March 2003. The results of an intensive visual stimulation program were retrospectively examined. Criteria were set to extract a fairly homogeneous group of 21 children with CVI due to perinatal HIE or postnatal anoxia who had extensive gray and white matter injury and multiple neurological deficits; 20 of 21 (95%) had symptomatic epilepsy as well. Subjects entered the study with responses ranging from just a pupillary light reflex to rudimentary perception of outline. Each subject underwent an at-home treatment program. Twenty of 21 children (95%) manifested significant improvement after 4 to 13 months on the program. Results indicate that even in this challenging group, there may be considerable neuroplasticity in visual systems leading to reintegration and visual recovery.

Distinct clinicopathologic subtypes of cortical dysplasia of Taylor

Two pathologic subtypes based on the presence or absence of balloon cells have been described in cortical dysplasia of Taylor (CDT). To determine whether the pathologic subtype has any distinct clinical or MRI features that are relevant to management. The histopathologic, clinical, and MRI features of 34 children with CDT who underwent epilepsy surgery at Miami Children's Hospital from 1990 to 2001 were investigated. Bizarre neuronal cytomegaly was the primary pathologic feature of 15 patients with the dysplasia-only subtype, and 19 cases showed additional characteristics including balloon cells and marked white matter abnormalities. Both groups presented with severe intractable epilepsy of very-early-onset, multiple daily seizures, cognitive disability, and focal neurologic deficits. The dysplasia-only subtype had higher rates of neonatal onset, hemiparesis, and severe mental retardation (p < 0.05). The MRI features of focal cortical thickening with associated cortical T2 signal change showed excellent sensitivity (94%) and reasonable specificity (73%) for the diagnosis of the balloon cell subtype. The overall surgical outcome was 59% seizure freedom at 2 years. Children with cortical dysplasia of Taylor type have in common a very-early-onset, severe epilepsy with neurologic co-morbidity. Patients with the non-balloon cell pathologic subtype have a more severe phenotype. A trend toward a better outcome in the balloon cell group suggests that preoperative identification of these subtypes may impact surgical planning.

Antiphospholipid Antibodies, Cocaine Use, and Stroke in a Young Woman

Stroke, which is unusual in young adults, has been linked to recreational drug use and the antiphospholipid syndrome (aPS). Cocaine use has been related to stroke in this population, and aPS is a known cause of thrombotic neurologic events. We report a patient with positive lupus anticoagulant and anticardiolipin antibodies as well as a history of cocaine use immediately preceding the acute onset of multiple neurologic deficits. The findings in this case suggest a relationship between the use of cocaine, the aPS, and stroke in young adults.

Neuronal loss from the subthalamic nuclei in a patient with progressive chorea

We present a case of an 80-year-old man who developed a seizure disorder at age 66 and was treated with chronic phenytoin. In the last 3 years of his life, he developed multiple neurological deficits, including bilateral chorea, ataxic gait, sensory neuropathy, and progressive dementia. After death from pneumonia, autopsy examination of the patient's brain was most remarkable for a selective loss of neurons from both subthalamic nuclei and Purkinje cell loss in the cerebellum. This pattern of injury is consistent with a toxic process and does not fit previously characterized pathological syndromes known to be associated with movement disorders or dementia or both. Phenytoin has been shown to cause choreiform movements, peripheral neuropathy, and cognitive decline in some patients, but the pathological basis for these changes has not been elucidated. The patient's chorea was very likely the result of neuronal loss in the subthalamic nuclei, but causes for his dementia and neuropathy were not found. The pathological findings may represent either an unusual form of chronic phenytoin toxicity or a previously undescribed primary degenerative brain syndrome.

Supranuclear Eye Movement Dysfunction in Mitochondrial Myopathy with tRNALEU Mutation

A patient with multiple neurological deficits and biopsy-proven mitochondrial myopathy with mutation of tRNA(LEU) at nucleotide 3243 was referred for eye movement evaluation. He had restricted range of voluntary motions in all directions and full range of eye movements on passive rotation of head while fixating a visual target. Eye movement recordings revealed decreased horizontal and vertical saccadic velocities and markedly decreased smooth pursuit gain in both directions. The vestibulo-ocular reflex showed gain abnormalities with many saccadic intrusions on the smooth reflex response. His brother, with similar mutation, was clinically asymptomatic. However, his eye movement recordings revealed slow horizontal saccadic velocities leftward and normal saccadic velocities rightward in both eyes as well as in upward and downward direction. Smooth pursuit and vestibulo-ocular reflexes were within normal limits. Although eye movement abnormalities are seen commonly in mitochondrial myopathies, the exact mechanism is not known. Our cases suggest supranuclear dysfunction as one of the mechanisms for ophthalmoparesis.

Four varied cases of intravascular lymphomatosis and a literature review

Intravascular lymphoma (IVL) is an uncommon malignancy defined pathologically by neoplastic proliferation of lymphoid cells within the lumens of capillaries, small veins, and arteries, with little or no adjacent parenchymal involvement. The nature of IVL has been the subject of considerable controversy. Recent immunohistochemical studies have demonstrated clearly that the tumors bear the immunophenotype of neoplastic lymphoid cells of either B-cell or T-cell lineage. IVL commonly affects the central nervous system, resulting in progressive dementia and multiple neurologic deficits; skin is the second most common site of involvement, in the form of cutaneous plaques and nodules. In a retrospective review of all cases of non-Hodgkin's lymphoma seen at our institution, four cases of IVL were identified. Case 1 was fixed in methacarin, and Cases 2-4 were fixed in 10% formalin. Standard fixation, tissue processing, sectioning, and hematoxylin and eosin staining were used. Immunophenotypic studies were performed using a modified avidin-biotin complex technique. The specimen in Case 1 was stained by Giemsa stain using standard techniques. Four cases of IVL are presented. One patient experienced hypoxemia and fevers of unknown origin; the second, dementia and a vasculitislike illness; the third rapidly progressive dementia, nonlocalizing neurologic deficits, and panhypopituitarism; the fourth Kaposi-like skin lesions. Case 1 relapsed shortly after completing chemotherapy. Salvage chemotherapy has yielded good initial response. Autopsy findings in cases 2, 3 and 4 confirmed IVL in many vessels, including the brain, lung, liver, heart, gastrointestinal tract, glomerulus, central nervous system, and skin. Malignant lymphoid cells marked as B-cells in all cases. Unusual and interesting clinical presentations may occur in patients with IVL. The medical literature indicates that few cases are diagnosed ante mortem. Although isolated patients may respond favorably to chemotherapy, most will deteriorate rapidly and the diagnosis of IVL not contemplated until necropsy.

18F]FDG PET in fatal familial insomnia

We used [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) to study regional cerebral glucose utilization (rCMRglc) in four patients with fatal familial insomnia (FFI), a prion disease with a mutation at codon 178 of the prion protein gene. Two patients, presenting only with insomnia and dysautonomia, had a prominent and, in one case, selective thalamic hypometabolism. The remaining two cases presented a more complex clinical picture with multiple neurologic deficits, with both thalamic and widespread brain hypometabolism involving the majority of cortical structures, basal ganglia, and the cerebellum. This widespread pattern was present in the early stage of the disease and showed significant worsening as the disease progressed in one patient examined twice. The thalamic hypometabolism, consistently found with PET in FFI patients, is in agreement with the neuropathologic findings and is a hallmark of the disease.

Sneddon's syndrome and pregnancy; a case report

The diagnostic and therapeutic problems posed by Sneddon's syndrome are discussed with reference to the case of a 31-year-old pregnant women. This patient developed episodes of cerebral ischemia with multiple neurological deficits in the 24th week of pregnancy. The symptoms were associated with the dermatological signs of livedo racemosa. Delivery by Cesarean section in the 36th week of pregnancy resulted in marked improvement of the neurological signs and symptoms.

Infantile autism: a syndrome of multiple primary deficits?

Attempts to explain infantile autism in terms of just one underlying neurological or psychological deficit may be misguided. As in the case of many neurological syndromes, autism may involve multiple functional deficits due to multiple coexistent neurological deficits. Comparison with Asperger's syndrome and the developmental dysphasias suggests that the autistic syndrome results from the coexistence of at least two distinct constellations of functional impairments: deficits in mechanical language skills, as in the developmental dysphasias; and deficits in social relatedness, play, and nonverbal communication, as in Asperger's syndrome. Possible neurological underpinnings are considered, including the relative contribution of the two cerebral hemispheres. Implications for etiology and research are discussed.

Rapid Development of Metastases from Basal Cell Carcinoma Presenting as Cranial Nerve Palsies

A case is reported of metastatic basal cell carcinoma presenting with multiple neurologic deficits 20 months after excision of the primary lesion with good local control. Many features associated with the development of metastasis from basal cell carcinoma were not present in this case.

4‐Aminopyridine improves clinical signs in multiple sclerosis

Twelve temperature-sensitive male patients with multiple sclerosis and 5 normal men were monitored before, during, and after the intravenous injection of 7 to 35 mg of 4-aminopyridine (4-AP) in 1- to 5-mg doses, every 10 to 60 minutes. Static quantitative perimetry, flicker-fusion frequency, visual acuity, and videotaped neurological examinations were performed. Ten of the 12 patients showed mild to marked improvement. Vision improved in 7 patients, oculomotor function in 5, and motor function (power, coordination, gait) in 5. Improvements developed gradually within minutes of drug injection at doses as low as 2 mg, and gradually reversed around 2 to 4 hours after the peak drug effect. No effects were observed in 5 patients given saline injections. No serious side effects occurred in either the normal subjects or the patients receiving 4-AP. It is concluded that 4-AP lessens multiple neurological deficits in multiple sclerosis and, furthermore, that the K+ channel is functional in demyelinated central nervous system axons in humans. The improvements with 4-AP are substantial enough to be of transient therapeutic benefit in selected patients.

Predictors of mortality and disability in stroke.

The increasingly accurate prediction of survival and functional recovery in patients with stroke will be of value in planning both their individual management and the health and social services needed. To establish the independent predictive effects of a range of personal and clinical characteristics, data on 900 patients admitted to Northwick Park Hospital with stroke were analysed by stepwise multiple regression. Older patients who lose consciousness at the outset and show signs of multiple neurological deficits, abnormal pupils, and conjugate deviation of the eyes are more likely to die within a year than those without these characteristics. Those who survive the acute episode and are discharged alive are more likely to die within a year if they are old and have sensory loss with severe physical disability. Older female patients who are incontinent, lose consciousness at the onset of stroke, sustain extensive motor deficits in combination with other neurological deficits, and have residual disabilities from previous strokes are particularly likely to be severely disabled on discharge from hospital. Routinely collected clinical data enable useful forecasts about mortality and disability after stroke. The accuracy of these forecasts can probably be improved further.

Rheumatoid Cervical Myelopathy

The mode of presentation and the factors which influenced the diagnosis and outcome in 31 patients with rheumatoid cervical myelopathy were reviewed. The presenting features included paraesthesiae and /or numbness (23 cases) weakness (six) flexor spasms (five) and incontinence (two). Isolated sensory loss presenting in a glove and stocking distribution was often misdiagnosed as a peripheral neuropathy. Multiple neurological deficits were eventually present in all patients and included spastic quadriparesis (17), spastic paraparesis (seven), bladder disturbance (nine), and cranial nerve deficits (six). Twenty-seven patients had impaired light touch and pin prick sensation but the sensory level did not correlate with the presumed level of spinal cord compressions. Twenty-one patients had dissociation between loss of position and vibration sensation. All patients had one or more cervical luxations; five patients had atlanto-axial luxation alone, five had subaxial luxation alone and the remainder multiple luxations. Neurological improvement was more frequent and of longer duration in those treated by occipito-cervical fusion than in those treated conservatively but fitness for surgery may have selected a group with a better prognosis.

Viruslike particles in granulomatous angiitis of the central nervous system

Neuropathologic examination of the brain of a 67-year-old woman with a 5-month history of progressive multiple neurologic deficits showed granulomatous angiitis of the small parenchymal and leptomeningeal blood vessels of the brain and spinal cord. Electron microscopy of formalin-fixed brain disclosed intranuclear viruslike particles resembling herpesvirus. Although definitive proof cannot be established without further virologic tests, this previously unreported finding suggests that some cases of granulomatous angiitis of the central nervous system may result from viral infection.