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Fiber-tracking does not accurately estimate size of fiber bundle in pathological condition: initial neurosurgical experience using neuronavigation and subcortical white matter stimulation.

The fiber-tracking method enables in vivo visualization of the white matter tracts of the brain using a diffusion tensor MR imaging technique. While this method represents a promising tool in the field of neurosurgery, especially when confronted with brain tumors in eloquent areas, its reliability remains unknown. We present here our preliminary validation of tractography in human subjects harboring brain tumors by comparing the results produced by neuronavigation and electrical white matter stimulation in two patients with gliomas in the eloquent area. Although we were able to visualize the pyramidal tract with the fiber-tracking technique, the images failed to present the actual size of the fiber bundles. Here we discuss the advantages and limitations of fiber-tracking in the field of neurosurgery.

Aged↗

Chronic progressive external ophthalmoplegia: MR spectroscopy and MR diffusion studies in the brain.

OBJECTIVE: The purpose of our study was to show how, despite pathognomonic signs of cerebral involvement in chronic progressive external ophthalmoplegia (CPEO), mitochondrial respiratory chain insufficiency is associated with increased lactate and reduced N-acetylaspartate. CPEO and mitochondrial myopathy are caused by mitochondrial DNA mutations leading to impaired oxidative phosphorylation. Cortical and subcortical metabolites, cerebral diffusivity, and structural MRI were assessed to characterize possible subclinical cerebral pathology in CPEO. SUBJECTS AND METHODS: Ten patients with CPEO (n = 8), mitochondrial myopathy (n = 1), and Kearns-Sayre syndrome (n = 1) and 13 control group volunteers were studied by MRI, both long TE (144) proton MR spectroscopic imaging (1H MRSI), and diffusion-weighted imaging. Relative concentrations of N-acetylaspartate, choline, creatine, and lactate were estimated by Linear Combination of Model Spectra (LCModel) in healthy-appearing white matter, gray matter, and white matter hyperintensities. RESULTS: Of five patients with cortical atrophy, it was moderate in three and severe in two. One patient had severe and four had moderate cerebellar atrophy. Six of 10 patients showed unspecific white matter lesions, whereas the remainder had hyperintensities in the pyramidal tract (n =2) and middle cerebellar peduncle (n = 1) despite clinical signs. No basal ganglia lesions were found. Physiologic metabolite ratios were normal and lactate was absent in supratentorial healthy-appearing cortex and subcortical white matter. Global diffusion histogram metrics revealed no abnormalities. CONCLUSION: Normal spectroscopic imaging in radiologic unaffected brain and healthy global brain parenchymal diffusion findings do not support the hypothesis of a generalized cerebral energy loss in CPEO. Bilateral structural alteration of central motor pathways in two patients without clinical pyramidal signs may, however, reflect subclinical axonal injury in predilection sites in some patients.

Adult↗

Adenosine A1 receptors mediate the inhibitory effects of exogenous adenosine in the rat olfactory cortex slice.

A study has been undertaken to identify the category of receptors mediating the inhibitory effects of adenosine on evoked activity in slices of olfactory cortex in the rat. The approach has been to measure the relative potencies of adenosine and a range of structural analogues [2-chloroadenosine, 2' deoxyadenosine, cyclohexyladenosine, (-)-5'N-ethyl-carboxamide adenosine and N6(L-2-phenylisopropyl)adenosine] required to: inhibit excitatory transmission at the lateral olfactory tract-pyramidal cell synapse; inhibit the specific binding of [3H]cyclohexyladenosine to membrane preparations and evoke formation of cyclic AMP. In contrast to the relative concentrations of the analogues necessary to increase levels of cyclic AMP, those required to inhibit synaptic transmission were characteristic of a selectivity for adenosine A1 receptors. The presence of adenosine A1 receptors has been demonstrated directly by characterizing the binding of [3H]cyclohexyladenosine to membranes prepared from slices of olfactory cortex. It is concluded that inhibition of transmission at the lateral olfactory tract-pyramical cell synapse by adenosine is mediated by receptors of the A1 category.

Adenosine↗

Central pontine myelinolysis.

Central pontine myelinolysis (CPM), a neurologic disorder caused most frequently by rapid correction of hyponatremia, is characterized by demyelination that affects the central portion of the base of the pons. There are no inflammatory changes, and blood vessels are normal. Clinical features usually reflect damage to the descending motor tracts and include spastic tetraparesis, pseudobulbar paralysis, and the locked-in syndrome. Magnetic resonance imaging of the brain, the imaging procedure of choice, shows an area of prolonged T1 and T2 relaxation in the central pons, which may have a characteristic shape. Recovery varies, ranging from no improvement to substantial improvement. To avoid CPM, correction of serum sodium in patients with hyponatremia should not exceed 12 mEq/24 h. We describe a case of CPM in a hyponatremic patient who presented with a cerebellar syndrome with no pyramidal tract involvement and in whom the rate of correction of serum sodium was within the recommended limits.

Humans↗

Multiple sclerosis and the urologist.

PURPOSE: We provide an updated reference detailing the neurological and urological state of the art approach to multiple sclerosis (MS) with special emphasis on the pathology and physiology, effects on the genitourinary tract, diagnostic evaluation, and treatment of neurological and urological manifestations. MATERIALS AND METHODS: A MEDLINE computerized reference search and manual bibliography review were performed to find pertinent peer reviewed articles on the neurological and urological manifestations and treatment of MS. A meta-analysis was performed on the urodynamic findings of 22 studies involving 1,882 patients from well-defined MS populations. RESULTS: The majority of patients with MS have genitourinary symptoms ranging from urgency, urge incontinence and frequency to urinary retention. Symptoms do not accurately reflect the underlying urological pathology but parallel pyramidal tract dysfunction. Urodynamic evaluation has an important role in determining proper bladder management. The most common urodynamic finding is detrusor hyperreflexia in 62% of these patients, followed by detrusor-sphincter dyssynergia in 25% and hypocontractility in 20%. Less than 1% of patients has renal deterioration and most may be treated with conservative measures. If conservative measures fail, new forms of bladder reconstruction and diversion may be effectively used. The incidence of sexual dysfunction is up to 80% in men and 72% in women, and treatment focuses on improvement of overall disability and erectile or orgasmic function. CONCLUSIONS: Although the genitourinary consequences of MS are rarely life threatening, they can cause significant morbidity and patient frustration. With the rapid advances in the medical management of MS the urologist should be actively involved in multispecialty treatment of these patients.

Female↗

Analysis of potentials induced in red nucleus neurones from the somaesthetic pathway stimulated at the bulbar level.

A somaesthetic pathway to the magnocellular red nucleus (RNm) via relays other than cortico- or cerebello-rubral relays was previously found to exist in the cat. At the brainstem level, the ascending spinorubral fibres follow the medial lemniscus (LM). The present paper aims at describing in detail and evaluating the quantitative importance of the short-latency responses in RNm cells after microstimulation performed in the LM through a monopolar electrode. The RNm cells, tested intracellularly in cats anaesthetized with alpha-choralose and placed in a stereotaxic device, were identified by their antidromic activation to stimulation of the rubrospinal tract in the cervical cord. It was established that single-shock stimulation below 100 miroA current delivered to the LM induced short-lantency postsynaptic potentials (PSPs) in 87% of all the rubrospinal cells tested. The responses were indeed due to activation of LM fibres, as demonstrated by different tests: the location of the electrode tip in the LM was verified by recording, with the same electrode, the potentials evoked by stimulating the dorsal columns of the cord. The site was later confirmed histologically. The absence of stimulus spread from the LM to the underlying pyramidal tract was systematically checked by simultaneously recording the responses evoked in RNm cells and in the motor cortex. Monosynaptic excitatory responses (EPSPs) were evoked in RNm cells with a minimum stimulating current of less than 20 microA in the LM and a mean threshold of 42 microA. Disynaptic inhibitory potentials (IPSPs) were evoked in 23% of these cells with single-pulse stimulation. These latter responses showed a temporal facilitation with short trains of three pulses, which indicated that they were transmitted through inhibitory interneurones. Recordings were also performed from presumed LM fibre terminals running inside the RNm. The results therefore confirm the existence of strong lemniscal projections to RNm and demonstrate that they transmit both excitatory and inhibitory messages to rubrospinal cells. As the somaesthetic pathway to the RNm was previously found to come from the spinal cord, where it is located in the ventral portion, the present results also confirm that the LM is composed of fibres originating not only from neurones in the dorsal column nuclei, but also from cells placed at the segmental levels of the cord. The presumed sensorimotor function of this ascending pathway is discussed.

Animals↗

Impaired cortico-bulbar tract function in dysarthria due to hemispheric stroke. Functional testing using transcranial magnetic stimulation.

We investigated cortico-lingual and cortico-orofacial tract function utilizing transcranial magnetic stimulation in 18 consecutive patients with dysarthria due to hemispheric stroke. Delayed responses (conduction time > mean + 2.5 SD of that of 43 controls) or absent responses were considered abnormal. In all patients, motor-cortex stimulation of the lesion side demonstrated absent (13 patients) or delayed (five patients) responses to the tongue bilaterally (17 patients) or unilaterally (one patient). In 14 patients the contralateral orofacial responses were either absent (13 patients) or delayed (one patient). According to the electrophysiological findings, all lesions revealed by CT or MRI, were located within the pyramidal tract at the lower motor cortex (n = 4), the corona radiata (n = 7), and the genu of the internal capsule (n = 3) or its posterior limb (n = 4). We conclude that interruption of the cortico-bulbar tract fibres to muscles involved in articulation is a frequent cause of dysarthria in hemispheric stroke.

Aged↗

An autoradiographic analysis of ascending projections from the medullary reticular formation in the rat.

Ascending projections from the several nuclei of the medullary reticular formation were examined using the autoradiographic method. The majority of fibers labeled after injections of [3H]leucine into nucleus gigantocellularis ascended within Forel's tractus fasciculorum tegmenti which is located ventrolateral to the medial longitudinal fasciculus. Nucleus gigantocellularis injections produced heavy labeling in the pontomesencephalic reticular formation, the intermediate layers of the superior colliculus, the pontine and midbrain central gray, the anterior pretectal nucleus, the ventral midbrain tegmentum including the retrorubral area, the centromedian-parafascicular complex, the fields of Forel/zona incerta, the rostral intralaminar nuclei and the lateral hypothalamic area. Nucleus gigantocellularis projections to the rostral forebrain were sparse. Labeled fibers from nucleus reticularis ventralis, like those from nucleus gigantocellularis, ascended largely in the tracts of Forel and distributed to the pontomedullary reticular core, the facial and trigeminal motor nuclei, the pontine nuclei and the dorsolateral pontine tegmentum including the locus coeruleus and the parabrachial complex. Although projections from nucleus reticularis ventralis diminished significantly rostral to the pons, labeling was still demonstrable in several mesodiencephalic nuclei including the cuneiform-pedunculopontine area, the mesencephalic gray, the superior colliculus, the anterior pretectal nucleus, the zona incerta and the paraventricular and intralaminar thalamic nuclei. The main bundle of fibers labeled by nucleus gigantocellularis-pars alpha injections ascended ventromedially through the brainstem, just dorsal to the pyramidal tracts, and joined Forel's tegmental tract in the midbrain. With the brainstem, labeled fibers distributed to the pontomedullary reticular formation, the locus coeruleus, the raphe pontis, the pontine nuclei, and the dorsolateral tegmental nucleus and adjacent regions of the pontine gray. At mesodiencephalic levels, labeling was present in the rostral raphe nuclei (dorsal, median and linearis), the mesencephalic gray, the deep and intermediate layers of the superior colliculus, the medial and anterior pretectal nuclei, the ventral tegmental area, zona incerta as well as the mediodorsal and reticular nuclei of the thalamus. Injections of the parvocellular reticular nucleus labeled axons which coursed through the lateral medullary tegmentum to heavily innervate lateral regions of the medullary and caudal pontine reticular formation, cranial motor nuclei (hypoglossal, facial and trigeminal) and the parabrachial complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Chronic progressive spinocerebellar syndrome associated with antibodies to human T-lymphotropic virus type I: clinico-virological and magnetic resonance imaging studies.

The relationship between HTLV-I infection and the development of spinocerebellar degeneration (SCD) in adulthood was studied. The frequency of anti-HTLV-I antibodies among patients with SCD (8 of 43, 19%) was found to be higher than the seroprevalence rate in the northern part of Kyushu island (6%). All HTLV-I carriers with SCD showed chronic progressive cerebellar ataxia as a predominant feature and cerebellar atrophy was evident in 6 of 8 patients on magnetic resonance imaging (MRI) of the brain. However, SCD patients with anti-HTLV-I antibodies showed a significantly higher frequency of cerebral white matter lesions on brain MRI (6 of 8) and pyramidal tract signs in lower extremities (6 of 8) than did those without the antibodies (35%, P < 0.05 and 26%, P < 0.01, respectively). Moreover, the HTLV-I carriers with SCD exceeded 14 HTLV-I carriers having neither SCD nor HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) (21%, P < 0.05), and 59 HTLV-I seronegative patients without brain disorders (19%, P < 0.001) in the frequency of white matter lesions. On the other hand, the HTLV-I carriers with SCD were distinct to the HAM/TSP patients in the predominance of cerebellar involvement. Therefore, the peculiar features of cerebellar, pyramidal and white matter involvement in the HTLV-I-seropositive SCD patients as well as the increased frequency of HTLV-I infection among SCD patients suggest that this syndrome may be a distinct subtype of HTLV-I-associated neurologic diseases.

Aged↗

Distribution of substance P-like immunoreactive fibres and terminals in the medulla oblongata of the human infant.

This study provides a detailed report of the distribution and density of substance P-like immunoreactive fibres and terminals within the human infant medulla. Seven brains with no signs of macroscopic alteration fixed usually within 24-48 h after death were used. Free floating transverse sections (50-60 microns) were then immunostained with a monoclonal antibody against substance P using the avidin-biotin-peroxidase technique. Morphologically three types of substance P-like immunoreactive fibres were observed: those with small varicosities of less than 1 micron, those with medium varicosities of 1-2 microns and those with large varicosities of 2-4 microns. Very dense substance P-like immunoreactivity was present within the spinal trigeminal nucleus, parts of the gracile and cuneate fasciculi and the paracommissural subnucleus of the solitary nucleus; dense substance P-like immunoreactivity was present within the dorsal nucleus of the vagus nerve, commissural, medial, dorsal, dorsolateral ventral and ventrolateral subnuclei of the solitary nuclear complex, parasolitary nucleus, raphe obscurus, inferior olivary complex (medial, dorsal, dorsomedial nuclei) and ventrolateral part of the dorsal reticular nucleus; moderate substance P-like immunoreactivity was present within the gelatinosus nucleus of the solitary tract, lateral reticular nucleus proper, intermediate reticular zone and parvocellular reticular nucleus; sparse substance P-like immunoreactivity was present within the hypoglossal nucleus, retroambigual nucleus and much of the reticular formation (dorsal, parvocellular, ventral gigantocellular, dorsal paragigantocellular nuclei): and very sparse substance P-like immunoreactivity was present within the nucleus ambiguus, medial vestibular nucleus and parts of the reticular formation (ventral, medial, gigantocellular, ventral gigantocellular, dorsal paragigantocellular nuclei). Substance P-like immunoreactivity was absent in the area postrema, intercalated nucleus, gracile and cuneate nuclei, in the epiolivary, subtrigeminal and parvocellular divisions of the lateral reticular nucleus, spinal vestibular nucleus, and in the solitary and pyramidal tracts. In several regions the substance P-like immunoreactive fibres formed distinct pericellular arrays around the somata and dendrites of neurons (hypoglossal nucleus, dorsal nucleus of the vagus nerve, retroambigual nucleus, intermediate reticular zone). The results indicate the high specificity of the localization of substance P in various structures of the brainstem and underline the presumed significance of this peptide in autonomic and sensorimotor functions of the brain.

Female↗

Autosomal dominant cerebellar ataxia type I. Nerve conduction and evoked potential studies in families with SCA1, SCA2 and SCA3.

Forty-one patients suffering from autosomal dominant cerebellar ataxia type I (ADCA-I) were subjected to a genotype-phenotype correlation analysis using molecular genetic assignment to the spinocerebellar ataxia type 1, 2 or 3 (SCA1, -2 or -3) genetic locus, clinical examination and nerve conduction as well as evoked potential studies. Pyramidal tract signs, pale discs, and dysphagia were more frequent in SCA1 compared with SCA2 and SCA3 patients, while double vision occurred less frequently. Visual evoked potentials and motor evoked potentials following transcranial magnetic stimulation were abnormal in almost all SCA1 patients, but only in a minority of SCA2 and SCA3 patients. In contrast, somatosensory evoked potentials were delayed or absent in the majority of patients with no significant differences between the mutations. Abnormalities of brainstem auditory evoked potentials were found in about half of the patients irrespective of the underlying mutation. In addition, reduced sensory nerve action potentials, suggesting sensory axonal neuropathy were found in all three mutations. These findings provide electrophysiological evidence that pyramidal and visual pathways are differentially affected in SCA1, SCA2 and SCA3 patients.

Action Potentials↗

Chronic asymmetrical spinal muscular atrophy.

The clinical and neurophysiological features of 18 cases of chronic asymmetrical spinal muscular atrophy are described. These were patients presenting with asymmetrical neurogenic atrophy involving one or more limbs who had no evidence of pyramidal tract dysfunction after 3 or more years of symptoms. There were twice as many males as females and the mean age of onset of the disorder was about 32 years. None of the patients had bulbar involvement. The tendon reflexes tended to be depressed. The distribution of muscle weakness in the limbs was very variable, and only slowly progressive. In 5 cases symptoms and signs were confined to the hands and forearms. Motor nerve conduction velocities to wasted muscles were slightly reduced but there was no evidence of generalised neuropathy. A diagnosis of chronic asymmetrical spinal muscular atrophy, as opposed to that of classical motor neurone disease, is favoured by an age of onset under 40 years, an absence of pyramidal signs or bulbar involvement after 3 years or more of symptoms, and depressed or absent tendon reflexes. The 2 conditions appear to be clinically distinct and prognosis is considerably better in chronic asymmetrical spinal muscular atrophy. The aetiology of this condition in unknown; it may be of relevance that 2 patients in this series had close relatives with Werdnig-Hoffmann disease.

Adult↗

Advanced neuronavigation in skull base tumors and vascular lesions.

OBJECTIVE: The purpose of this study was to describe the usefulness of recent advances of neuronavigational technology in the management of skull base tumors and of vascular lesions, treated via a skull base approach. METHODS: In 16 patients (skull base meningioma n = 9, petrous apex epidermoid n = l, craniopharyngeoma n = 1, giant internal carotid artery aneurysm n = 1, basilar/vertebral artery aneurysm n = 2, brain stem cavernoma n = 2), "advanced" neuronavigation was used. In contrast to "conventional" neuronavigation, the information for the neurosurgeon was enhanced by the intraoperative screen display of 3-dimensional reconstructions of the lesion, vessels, nerves and fiber tracts at risk. The 3-dimensional reconstructions were obtained by preoperative manual or automated segmentation processes. In addition, different imaging modalities (computed tomography [CT] with magnetic resonance imaging [MRI], CT with CT angiography, T (l)- with diffusion-weighted MRI) were fused and shown on the screen. RESULTS: In the cases of tumors, "advanced" neuronavigation facilitated the approach (n = 4), contributed to tailor the approach (n = 2) and helped to identify hidden neurovascular structures (n = 9). In the cases of aneurysms, "advanced" neuronavigation allowed us to reduce the skull base approach to the needs of safe aneurysm clipping (n = 3). In both cases of brain stem cavernoma, "advanced" neuronavigation was deemed useful for definition of the best surgical approach in relation to the pyramidal tract and brain stem nuclei. CONCLUSION: The authors' experiences suggest that neuronavigation, which displays 3-dimensional reconstructions of lesion, vessels, nerves and fiber tracts during surgery and makes use of image fusion techniques, is an important tool in the neurosurgical management of skull base lesions.

Adolescent↗

Characterization of microglial reaction after middle cerebral artery occlusion in rat brain.

We have studied the microglial reaction that accompanies cortical infarction induced by middle cerebral artery occlusion (MCAO). Lectin histochemistry with the B4-isolectin from Griffonia simplicifolia as well as immunocytochemistry with a panel of monoclonal antibodies directed against major histocompatibility complex (MHC) and lymphocytic antigens were performed. Principal attention was focused on neocortical and thalamic regions, representative of primary and secondary ischemic damage, respectively. With the lectin procedure, activated microglial cells were abundant in the neocortex 24 hours after MCAO. In contrast, microglial activation in the thalamus was not apparent until day 2 after MCAO. On day 5, MHC class II antigen was expressed by reactive microglia in fiber tracts traversing the striatum, but was absent from activated microglia in the primary cortical infarction area. MHC class I and lymphocytic antigens were expressed differentially on microglia with class I antigens appearing early and lymphocytic antigens appearing late in the time course after focal ischemia. The findings are compatible with previous studies during global ischemia and confirm the early activation and the progressive nature of immunomolecule expression on activated microglia after an ischemic insult. In addition to neocortical and thalamic sites, our results showed an early microglial activation to be present also in forebrain regions outside of the middle cerebral artery (MCA) territory, such as the contralateral cortex and hippocampus. A unilateral microglial reaction was also detectable after long-term survival (> or = 4 weeks) in the pyramidal tracts, as well as in the corticospinal tracts at cervical but not lumbar spinal cord levels. Ischemia-induced neuronal damage, as evaluated by Nissl staining, was found only in cortical and thalamic regions. We conclude that the demonstration of reactive microglia indicates not only imminent ischemic neuronal damage within MCA territory but can also delineate extra-focal disturbances, possibly reflecting subtle and transitory changes in neuronal activity.

Animals↗

Spinal cord axonal loss in multiple sclerosis: a post-mortem study.

There is increasing interest in the contribution that axonal damage may make to clinical disability in multiple sclerosis (MS). The present study reports a post-mortem examination of the area occupied by the lateral white matter columns of the spinal cord and nerve fibre density in the corticospinal tracts at C3 and T2 in 23 males and 20 females with MS, who lacked plaques at these levels, and in 31 controls who, although most had had some neurological disease, showed no sign of cervical or spinal cord thoracic disease. The lateral column cross-sectional area, measured by low power image analysis of the outlined lateral columns, was reduced in MS by 17% at C3 and 21% at T2 in males and by 13% at C3 and 18% at T2 in females. These reductions were significant at both levels in males (P<0.004 at C3 and P<0.009 at T2 ) but only at T2 in females (P<0. 03). The nerve fibre density, measured by automatic image analysis of x200 microscopic fields in the region occupied by the crossed pyramidal tracts, was reduced by 41% at C3 and 42% at T2 in males and by 19% at both C3 and T2 in females. These reductions were likewise significant at both levels in males (P<0.003 and P<0.000 at C3 and T2, respectively) and T2 only in females (P<0.045). In MS, nerve fibre density was significantly lower at C3 (P<0.004) and T2 (P<0.000) in males than females. No differences were seen in these parameters between males and females in controls. The reductions in total nerve fibre densities were entirely accounted for by reductions in small nerve fibres (cross sectional area less than 5 microm2 ). No significant reductions were seen in large fibre (cross sectional area 5 microm2 or more) densities. It is concluded that substantial axonal loss and spinal cord lateral column white matter atrophy occur at C3 and T2 in MS, and that these changes can be detected in some patients from early in the course of the disease.

Adult↗

Intraputamenal infusion of GDNF in aged rhesus monkeys: distribution and dopaminergic effects.

Site-specific delivery of trophic factors in the brain may be important for achieving therapeutic efficacy without unwanted side effects. This study evaluated the site-specific infusion of glial cell line-derived neurotrophic factor (GDNF) into the right putamen of aged rhesus monkeys. After 4 weeks of continuous infusion at a rate of 22.5 microg/day, GDNF had diffused up to 11 mm from the catheter openings in the putamen into the rostral putamen, internal capsule, external capsule, caudate nucleus, and globus pallidus. Anisotropic flow along the external capsule tracts carried GDNF into the anterior amygdaloid area. Backflow of GDNF along the catheter track from the frontal cortex infiltrated juxtaposed corpus callosal and cortical tissue. GDNF was carried by retrograde transport to dopamine neurons in the ipsilateral substantia nigra, stimulating an 18% increase in the number of tyrosine hydroxylase (TH)-positive dopamine neurons and a 28% increase in dopamine neuron perikaryal size. Also, TH-positive fiber density was increased in the ipsilateral globus pallidus, caudate nucleus, and putamen. Anatomic effects from GDNF stimulation of the dopaminergic system were restricted to the ipsilateral hemisphere. Retrograde GDNF labeling was also present in a few TH-positive neurons in the locus coeruleus and a large cluster of TH-negative neurons in the ventral anterior thalamus. Anterograde transport of GDNF was evident in axons in the pyramidal tract from the cerebral peduncle to the caudal spinal cord. Tissue injury from the intraparenchymal catheter and continuous infusion was confined primarily to a narrow zone surrounding the track and was mild to moderate in severity.

Aging↗

[A 49-year-old man with progressive bulbar palsy and respiratory failure].

We report a 49-year-old man with progressive bulbar palsy and respiratory failure. He was well until his 48 years of the age (December 1994) when he noted a difficulty in speaking in loud voice. In February, 1995, he noted regurgitation of foods to his nose and difficulty in his speech. He was admitted to our service in May 29, 1995. On admission, he was alert and oriented to all spheres and he was not demented. His higher cerebral functions were normal. In cranial nerves, he showed dysarthria and dysphagia; muscle atrophies were seen in the tongue, the bilateral sternocleidomastoid, supraspinatus, and infraspinatus muscles. Fasciculations were seen in these muscles. He showed no muscle weakness in his limbs except for the upper limb girdle muscles, no ataxia, no reflex abnormalities, nor sensory changes. EMG showed neurogenic changes in the affected muscles. MRI of the brain and the spinal cord was entirely normal. He was discharged for out patient follow-up, however, in October of 1995, he noted difficulty in swallowing solid foods. Gastrostomy was placed and he was discharged to his home. In February 11th of 1996, he was found unresponsive and brought into the ER of our hospital. On admission, he was comatose without spontaneous respiration. BP could not be obtained. He was immediately intubated and artificial ventilation was started. On the following morning, he became alert and he was not demented. He continued to show marked dysarthria and dysphagia; again no weakness was noted in the distal parts of the upper and lower extremities. Laboratory examination showed increase in serum CK to 2,173 IU/L and amylase to 2,032 IU/L. He was extubated on February 15th, however, his spontaneous respiration was not suffice to maintain his blood gas. According to his will, he was not placed on respirator and he died on February 24th, 1996. The patient was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had ALS. Although no upper neuron signs were observed clinically, it is not uncommon to see degeneration in the corticospinal tract in post-mortem examination. The question was what might have been the cause of increase in CK and amylase. Many participants thought that they were secondary to multiple organ failure due to prolonged hypoxic state at his last admission; other possibilities raised included acute myocardial infarction and acute bowel necrosis. Post-mortem examination revealed muscle atrophy in the facial, lingual, cervical, intercostal, and the upper limb girdle areas. The lungs were unremarkable except for old organized pneumonic foci in the right middle and lower lobes. Marked to moderate congestion was seen in many internal organs, however, no other gross abnormality was found. It was thought that respiratory palsy itself was the direct cause of his agonal event. In the spinal cord, the anterior horns showed various degree of neuronal loss and gliosis. No clear evidence of pyramidal tract degeneration was seen at the light microscope level. Lower brain stem motor neurons were markedly reduced. But no Bunina body was found. The substantia nigra showed moderate degree of neuronal loss and extraneuronal neuromelanins. The locus coeruleus showed similar but milder changes. The degree of nigral degeneration appeared to be well beyond those which could be seen in usual ALS patients. The question was whether or not this patient might have been in an early stage of the extended form of ALS.

Amyotrophic Lateral Sclerosis↗

Neocortical pyramidal cells: a model with dendritic calcium conductance reproduces repetitive firing and epileptic behavior.

A computer model of a neocortical pyramidal cell has been constructed using ideas similar to those used for hippocampal pyramidal cells. This model has been applied to the study of (a) repetitive firing, and (b) the paroxysmal depolarizing shift (PDS), an important intracellular event during seizures. Although calcium spikes have not been demonstrated directly in neocortical cells, we have postulated (by analogy with hippocampal pyramidal cells) a dendritic calcium conductance and a 'slow potassium' conductance modulated by intracellular calcium ion. With these dendritic ionic conductances, the model is able to reproduce the following experimental features of neocortical pyramidal cells: the afterdepolarization and succeeding afterhyperpolarization after an antidromic spike, and the f-I (firing rate-injected current) curve. Some of the differences between 'fast' and 'slow' pyramidal tract neurons (PTNs) -- narrower spikes and a steeper f-I curve in the fast PTNs -- may be explained by differences in Hodgkin-Huxley potassium kinetics between the two kinds of cell. The same model which faithfully reproduces repetitive firing behavior also reproduces (given appropriate synaptic inputs) the following intracellular events recording during epileptic seizures: (a) a burst of action potentials superimposed on and followed by a PDS, and (b) rapid repetitive firing succeeded by an IPSP. Thus, a single set of parameters can reporduce both normal physiological behavior and 'epileptic' behavior: the particular behavior seen depending on how the cell is stimulated. This overall result is the same as for our model of the CA1 hippocampal cell. It suggests that certain acutely acting epileptogenic agents, e.g. penicillin, may act by increasing synaptic input (perhaps both excitatory and inhibitory) to pyramidal cells, rather than by altering their membrane properties. As in our CA1 hippocampal cell model, bursting seems to be a phenomenon generated by the apical dendrite.

Biophysical Phenomena↗