Ultrastructure and immunohistochemistry of the trigeminal peripheral myelinated axons in patients with neuralgia

Objective

Detailed ultrastructural and immunohistochemical examination of the trigeminal axons surrounded by the peripheral type of the myelin could add new information about the extent of the trigeminal nerve lesion in neuralgia.

Patients, materials and methods

The examination comprised, firstly, the 10 trigeminal nerve roots (TNRs) in which the neurovascular contact was found in 20% of the cases, and the 2 additional control TNRs. Secondly, the biopsy specimens were taken from 6 patients with trigeminal neuralgia and 2 patients with trigeminal neuropathy following a partial TNR rhizotomy. The specimens were examined under the electron microscope (EM) and/or using the immunohistochemical (IHC) methods.

Results

In addition to the central zone of demyelination, the EM examination of the TNR also revealed alterations of the peripheral myelin, i.e. deformation, thickening, demyelination and remyelination, as well as changes of the peripheral axons, that is, atrophy or hypertrophy, neurofilaments increase, loss of the myelin and sprouting occasionally. Some Schwann cells were also damaged. The IHC examination usually showed a moderate immune reaction against neuron-specific enolase (NSE) and protein gene product 9.5 (PGP9.5), but sporadically weaker reaction against the S-100 protein, synaptophysin (SY), neurofilament protein (NFP) and glial fibrillary acidic protein (GFAP). The substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactivity was weak at some sites, but strong at some other places.

Conclusions

The pathological changes affect not only the central nerve fibers of the TNR, but also some of the peripheral axons, their myelin sheath and Schwann cells. These are signs of the retrograde ultrastructural and biochemical alterations, which could participate in the pathophysiological mechanism underlying the trigeminal neuralgia.     

Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey.

In the rhesus monkey, the myelin sheaths of nerve fibers in area 46 of prefrontal cortex and in splenium of the corpus callosum show age-related alterations in their structure. The alterations are of four basic types. Most common is splitting of the dense line of myelin sheaths to accommodate electron dense cytoplasm derived from the oligodendroglia. Less common are splits of the intraperiod line to form balloons or blisters that appear to contain fluid, the occurrence of sheaths with redundant myelin, and thick sheaths that are almost completely split so that one set of compact lamellae is surrounded by another set. But despite these alterations in the sheaths, few nerve fibers show axonal degeneration. To quantify the frequency of the age-related alterations in myelin, transversely sectioned nerve fibers from the splenium of the corpus callosum and from the vertical bundles of nerve fibers within area 46 were examined in electron photomicrographs. The material was taken from 19 monkeys, ranging between 5 and 35 years of age. It was found that the frequency of alterations in myelin sheaths from both locations correlates significantly with age. In area 46, the age-related alterations also significantly correlate (P < 0.001) with an overall assessment of impairment in cognition, i.e., the cognitive impairment index, displayed by individual monkeys. The correlation is also significant when only the old monkeys are considered as a group. A similar result was obtained previously in our examination of the effects of age on the myelin sheaths of nerve fibers in primary visual cortex (Peters et al. [2000] J Comp Neurol. 419:364-376). However, in the corpus callosum the myelin alterations correlate significantly with only one component of the cognitive impairment index, namely the delayed nonmatching to sample task with a 2-minute delay. It is proposed that age-related myelin alterations are ubiquitous and that the correlations between their frequency and impairments in cognition occur because the conduction velocity along the affected nerve fibers is reduced, so that the normal timing sequences within neuronal circuits break down.     

Acute effect of callosotomy on cortical temporal coupling in humans: Intraoperative electrocorticographic recording

Objective

To investigate the acute role of the corpus callosum in inter- and intrahemispheric temporal coupling.

Methods

Intraoperative electrocorticography (ECoG) makes it possible to investigate the acute role of the corpus callosum in cortical temporal coupling, or synchrony, without additional surgical intervention, thus avoiding the confounding effects of scalp recordings and the long-term reorganization of functional connectivity. ECoGs were recorded in three patients during callosotomies. Bilateral electrode grids were placed over the frontal cortex. ECoGs were recorded immediately before and after performing the anterior two-thirds callosal transection, were digitalized at a sampling rate of 512 Hz, inspected for artifacts, and later analyzed offline. Cross-correlation between inter- and intrahemispheric electrode pairs were obtained for 1 Hz bins and special broad bands obtained by principal component analysis for each patient pre- and post-callosotomy.

Results

A statistically significant change was observed in intrahemispheric temporal coupling between electrode pairs that exceeded the confidence limit of correlation.

Conclusions

Present results show that interrupting the influence of the corpus callosum has an acute effect on intrahemispheric activity by decreasing temporal coupling between cortical areas.

Significance

Intrahemispheric temporal coupling does not depend exclusively on ipsilateral cortico-cortical pathways or on subcortical influences, but also on callosal pathways.     

Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study

Background

Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions.

Objective

To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age‐related white matter hyperintensities (WMH).

Methods

In the Leukoaraiosis and Disability Study, 567 subjects with age‐related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors.

Results

Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing—namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion.

Conclusions

Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal‐lobe‐mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.Corpus callosum is the largest commissural structure consisting of white matter tracts that connect the cerebral hemispheres according to an anterior–posterior topographical organisation. Recent research using diffusion tensor magnetic resonance imaging (MRI) has augmented earlier postmortem findings of corpus callosum topography and has shown that the anterior parts of corpus callosum (rostrum and genu) connect the orbitofrontal, lateral and medial frontal cortices, whereas the body and splenium connect parietal, temporal and occipital homotopic regions.¹ In neurodegenerative diseases, the corpus callosum area is markedly reduced, indicating marked axonal loss.^2,3,4,5 In Alzheimer''s disease, the severity and pattern of corpus callosum atrophy have been associated with cortical neuronal loss⁶ independently of white matter hyperintensities (WMH).⁷ In vascular dementia and other ischaemic conditions, however, corpus callosum atrophy is correlated with WMH and hence may result from subcortical ischaemic damage.^8,9Earlier studies have shown that corpus callosum atrophy is associated with global cognitive status,^5,6,10 but, to date, few studies have investigated the role of regional corpus callosum atrophy in specific cognitive processes. Based on the topographical organisation of corpus callosum, the integrity of its subregions may reflect distinct cognitive deficits. In particular, anterior corpus callosum atrophy may be related to the frontal‐lobe‐mediated executive deficits. Previous work of the Leukoaraiosis and Disability (LADIS) Study has shown that age‐related WMH are associated with cognitive impairment in elderly subjects without dementia.¹¹ Moreover, in these subjects, the corpus callosum area has been found to be inversely related to motor deficits and global cognitive decline.¹² This study examined the independent contribution of regional corpus callosum atrophy to deficits in mental speed, attention and executive functions in a large sample of elderly subjects with WMH by using quantitative MRI analysis and targeted neuropsychological test methods. The demographic and medical background variables, and coexisting WMH were controlled by using multivariate analysis.     

Time-varying inter-hemispheric coherence during corpus callosotomy

Objective

Corpus callosotomy limits the bilateral synchrony of epileptic discharges. However, the instantaneous changes in bilateral synchrony during corpus callosotomy are unclear. The present study investigated how and when bilateral synchrony is suppressed in the anterior and then posterior steps of corpus callosotomy.

Methods

Intra-operative scalp electroencephalography (EEG) was recorded simultaneously with surgical video for six patients who underwent total corpus callosotomy for medically intractable drop attacks. The time-varying EEG inter-hemispheric coherence was quantified by wavelet transform coherence and trend analysis.

Results

The 4–13 Hz coherence decreased after corpus callosotomy in five patients. Significant decrease in coherence was observed only during the posterior step of callosal sectioning in three patients, but throughout both steps in two patients.

Conclusions

Decrease in inter-hemispheric coherence is not always correlated with the stages of callosal sectioning. Inter-hemispheric coherence is decreased during the final stage of corpus callosotomy and the effect is maximized after sectioning is completed.

Significance

Various patterns of coherence decrease suggest individual variations in the participation of the corpus callosum in the genesis of bilateral synchrony. Time-varying inter-hemispheric EEG coherence is useful to monitor the physiological completeness of corpus callosotomy.     

Frequency-dependent conduction block in ulnar neuropathy localized to the elbow

Objective

To determine whether frequency-dependent conduction block (FDB) occurs in acute ulnar neuropathies localized to the elbow.

Methods

High-frequency nerve stimulation (30 Hz, 20 stimuli) was applied to the ulnar motor nerve above and below the elbow in controls (15) and in patients with short duration (between 2 and 16 weeks) ulnar neuropathy localized to the elbow (10) with evidence of moderate to severe conduction block and slowing.

Results

FDB was not observed in any of the 10 subjects tested. Three of these subjects were seen in follow-up; studies in two of these subjects, during the recovery period, did however demonstrate FDB with a similar pattern to that observed previously in CTS.

Conclusions

This study has demonstrated that the remaining unblocked ulnar motor fibers across the elbow in acute ulnar neuropathy with conduction block, do not demonstrate FDB in response to stimulation at 30 Hz.

Significance

These results suggest that FDB may not occur in the unblocked fibers in ulnar neuropathy despite evidence of conduction slowing. These results differ from previous observations in CTS and imply that demyelinating lesions (conduction block versus slowing) respond differently to high-frequency stimulation.     

Increased variability of axonal excitability in amyotrophic lateral sclerosis

Objective

Amyotrophic lateral sclerosis (ALS) is characterised by the increased excitability of motoneurons and heterogeneous loss of axons. The heterogeneous nature of the disease process among fibres may show variability of excitability in ALS.

Methods

Multiple nerve excitability tests were performed in 28 ALS patients and 23 control subjects, by tracking at the varying threshold levels (10%, 20%, 40% and 60% of maximum amplitudes).

Results

In normal controls, excitability measures at low target levels have the following characteristics compared to those at high target levels: longer strength–duration time constant, greater threshold reduction during depolarising currents and smaller threshold increase to hyperpolarising currents. ALS patients had less clear amplitude dependency of the parameters than the controls, indicating variability of axonal excitability. Three ALS patients demonstrated greater target-amplitude-dependent threshold changes in threshold electrotonus than controls, suggesting selective axonal hyperexcitability.

Conclusions

Some of the ALS patients had variable axonal excitability at different target amplitudes, suggesting preferential hyperexcitability in the axons with low target amplitude levels.

Significance

Variable membrane potentials of motor axons in ALS may be assessed by recording excitability testing at different target amplitude levels.     

Caprine beta-mannosidosis: development of glial and myelin abnormalities in optic nerve and corpus callosum

In caprine beta-mannosidosis, an inherited dysmyelinating disorder, the myelin deficit shows substantial variation throughout the nervous system. In this study morphometric analysis of optic nerve and corpus callosum sections at selected developmental stages was conducted in order to investigate development and persistence of myelin sheaths, the population of axons ensheathed, and the extent of myelin deficits and glial cell abnormalities. The results show that the myelin deficit is severe at very early stages of development and persists to about the same extent into postnatal life. The corpus callosum, much more severely involved than the optic nerve, contains a substantially smaller percentage of myelinated axons when compared to control. In both regions, larger axons are preferentially myelinated. In the corpus callosum before myelination begins, many glial cells appear abnormal, suggesting an early cellular defect. In the postnatal, myelin-deficient corpus callosum, there is a substantial decrease in glial cell density as compared to control, with abnormal appearance of many of the remaining cell profiles. These results define developmental characteristics of the dysmyelination in caprine beta-mannosidosis and document both the early appearance and the persistence of glial cell body and myelin abnormalities.     

Abnormal brain MRI signal in 18q-syndrome not due to dysmyelination

Background

18q-Syndrome is a chromosomal disorder exhibiting various symptoms arising from the central nervous system. Brain magnetic resonance imaging (MRI) of patients with this syndrome usually demonstrates abnormal white matter intensities. This is widely believed to be due to impaired myelin formation because this syndrome involves the deletion of the myelin basic protein (MBP) gene in 18q23. However, this hypothesis has not been confirmed by actual pathology because early death is unusual and autopsy rarely performed.

Patient

A 6-year-old boy with ring chromosome 18 syndrome was examined by genetic analysis for the MBP gene, brain MRI, and autopsy.

Results

Haploinsufficiency of the MBP gene was confirmed. T₂-weighted MRI revealed diffuse high intensities throughout the cerebral white matter. Pathological examination showed the cerebral white matter to be uniformly stained by Klüver–Barrera and MBP immunohistochemical staining. Oligodendrocytes were immunoreactive for proteolipid protein and ferritin but not MBP. Electron microscopy revealed clusters of axons wrapped in compact myelin sheaths with distinct major dense lines. Holzer and immunohistochemical staining for glial fibrillary acidic protein showed extensive staining of the white matter and an increased number of glial filaments.

Conclusions

This pathological study demonstrated that in this disorder, the brain was well myelinated, contrary to established hypotheses about this disorder. The MRI signal abnormalities in 18q-syndrome could be attributed to gliosis and not to dysmyelination.     

A correlative light and electron microscopic study of postnatal myelination in the murine corpus callosum

Oligodendroglial cells differ in their ultrastructural appearance depending on their myelin producing and maintaining activity. To better understand the relationship between light and electron microscopic features of myelination, myelin formation in the corpus callosum was studied in young postnatal mice. Immunostaining for myelin basic protein (MBP), which has an important role in myelin compaction, was compared with conventional Luxol Fast Blue myelin staining and with electron microscopic images of unlabeled tissue. MBP-immunostaining labeled a few oligodendroglial cells at postnatal day (P)3, and a few axons at P7 in the corpus callosum, below the fronto-parietal somatosensory cortex. By P10 there were more myelinated axons below the somatosensory cortex and the first MBP-immunoreaction appeared in the cingulum: labeling appeared even later in the remaining areas of corpus callosum. Electron microscopy revealed numerous medium oligodendroglial cells at P7 in the corpus callosum, below the somatosensory cortex with the first sign of myelination at P10. By P14, there were numerous myelin sheaths with loosely built structure, and the number of myelin sheaths increased continuously thereafter. However, even as late as P28, the presence of both thick, compact and thin, loosely structured myelin sheaths in the same section suggested ongoing myelination. With Luxol Fast Blue myelin staining was first observed in the corpus callosum relatively late, at P14. Areal differences in myelination of the corpus callosum, seen with MBP-immunohistochemistry, indicate that myelin formation follows cortical maturation rather than the rostro-caudal developmental growth of the corpus callosum. Myelination of the afferent and efferent fibers within the cortical areas seems to follow the inside-out maturational pattern of cortical neurons, with the first myelinated axons always appearing in layers V-VI. In addition to the known neuronal and astroglial factors that regulate myelin formation by oligodendroglial cells, we suggest that these cells and their myelin covering may also influence axonal maturation. Light microscopic data obtained with MBP-immunohistochemistry correlates well with electron microscopic observations but not with Luxol Fast Blue staining which reveals myelinated axons only relatively late in development. Therefore, both MBP-immunostaining and electron microscopy are useful, alone or in combination, for the detection of myelination, demyelination as well as remyelination processes in animal models and also in humans.     

Evidence for white matter disruption in traumatic brain injury without macroscopic lesions

Background

Non‐missile traumatic brain injury (nmTBI) without macroscopically detectable lesions often results in cognitive impairments that negatively affect daily life.

Aim

To identify abnormal white matter projections in patients with nmTBI with cognitive impairments using diffusion tensor magnetic resonance imaging (DTI).

Methods

DTI scans of healthy controls were compared with those of 23 patients with nmTBI who manifested cognitive impairments but no obvious neuroradiological lesions. DTI was comprised of fractional anisotropy analysis, which included voxel‐based analysis and confirmatory study using regions of interest (ROI) techniques, and magnetic resonance tractography of the corpus callosum and fornix.

Results

A decline in fractional anisotropy around the genu, stem and splenium of the corpus callosum was shown by voxel‐based analysis. Fractional anisotropy values of the genu (0.47), stem (0.48), and splenium of the corpus callosum (0.52), and the column of the fornix (0.51) were lower in patients with nmTBI than in healthy controls (0.58, 0.61, 0.62 and 0.61, respectively) according to the confirmatory study of ROIs. The white matter architecture in the corpus callosum and fornix of patients with nmTBI were seen to be coarser than in the controls in the individual magnetic resonance tractography.

Conclusions

Disruption of the corpus callosum and fornix in patients with nmTBI without macroscopically detectable lesions is shown. DTI is sensitive enough to detect abnormal neural fibres related to cognitive dysfunction after nmTBI.Cognitive and vocational sequelae are common complications after non‐missile traumatic brain injury (nmTBI) without obvious neuroradiological lesions.^1,2 They may present as memory disturbance, impairments in multitask execution and loss of self‐awareness.³ These symptoms have been attributed to diffuse brain injury and the diffuse loss of white matter or neural networks in the brain.^4,5,6 Currently no accurate method is available for diagnosing and assessing the distribution and severity of diffuse axonal injury. As computed tomography and magnetic resonance imaging (MRI) findings underestimate the extent of diffuse axonal injury and correlate poorly with the final neuropsychological outcome,^7,8 this dysfunction tends to be clinically underdiagnosed or overlooked. Indirect evidence for loss of functional connectivity after nmTBI has been provided by both morphometric and functional neuroimaging studies. Morphometric analysis of nmTBI has shown the relationship between atrophy of the corpus callosum and fornix and the neuropsychological outcome.⁹ Most functional neuroimaging studies conducted after nmTBI have shown that cognitive and behavioural disorders are correlated, with some degree of secondary hypometabolism or hypoperfusion in regions of the cortex.⁵ To date, however, there has been no direct in vivo demonstration of structural disconnections without macroscopically detectable lesions in patients with nmTBI.Diffusion tensor magnetic resonance imaging (DTI), which measures diffusion anisotropy in vivo, is a promising method for the non‐invasive detection of the degree of fibre damage in various disease processes affecting the white matter.^10,11 In biological systems, the diffusional motion of water is impeded by tissue structures, such as cell membranes, myelin sheaths, intracellular microtubules and associated proteins. Motion parallel to axons or myelin sheaths is inhibited to a lesser degree than perpendicular motion, a phenomenon known as diffusion anisotropy.¹² Fractional anisotropy was applied to evaluation of post‐traumatic diffuse axonal injury¹³ and its clinical usefulness described. In a previous study,¹⁴ fractional anisotropy score in the acute stage as an index of injury to white matter showed promise in predicting outcome in patients with traumatic brain injury, by using the regions of interest (ROIs) techniques. MRI voxel‐based analysis, a statistical normalising method, has been developed to reduce interindividual variability and to evaluate the whole brain objectively.^15,16,17 We investigated the regions in the whole brain that are commonly injured in patients having nmTBI with cognitive impairments but no macroscopic lesions, using voxel‐based analysis of fractional anisotropy, referred to as diffusion anisotropy. The advent of DTI has allowed inter‐regional fibre tracking, called magnetic resonance tractography, which reconstructs the three‐dimensional trajectories of white matter tracts.^11,18,19 We also investigated whether magnetic resonance tractography sensitively recognises degeneration of the corpus callosum and fornix in individual patients with nmTBI.     

The differential yet concurrent contributions of motor,cognitive and affective disturbance to freezing of gait in Parkinson's disease

Objectives

We sought to concurrently examine the specific motor, cognitive and affective contributions to self-reported FOG symptoms.

Patients and methods

Ninety-six patients with Parkinson's disease completed the validated freezing of gait questionnaire and had their motor function scored on section three of the Unified Parkinson's Disease Rating Scale questionnaire. A 5-choice reaction time task was administered in order to measure cognitive processing speed and the Beck Depression Inventory was utilised to assess affective disturbance.

Results

The results showed that after controlling disease duration and dopaminergic medication dose, the triad of motor disability, cognitive processing speed and affective symptoms were all significant independent predictors of scores on the freezing of gait questionnaire.

Conclusions

These findings suggest the need to consider the interplay between distinct motor, cognitive and affective domains in aetiological studies of freezing and the development of future therapies.     

Muscle and nerve biopsies: Techniques for the neurologist and neurosurgeon

Objective

Muscle and nerve biopsies are commonly performed procedures for the diagnosis of neuromuscular disorders. Neurologists and neurosurgeons are often consulted to perform these procedures in clinical practice. We provide guidelines in the performance of muscle and nerve biopsies.

Methods

We describe the technique for performance of muscle and nerve biopsy, and review the relevant literature.

Results

The quadriceps muscle is the most typical biopsy site for most myopathies, whereas the sural nerve is the most common nerve biopsy site for most peripheral neuropathies. Other sites may be utilized depending upon the pattern of symptoms or the differential diagnosis. Motor nerves may be sampled in the setting of motor neuron disease, for example. We advocate the use of conduit repair to allow for sensory or motor recovery to occur following nerve biopsy.

Conclusion

The muscle biopsy and nerve biopsy may be performed with high yield, low morbidity, and rare complications.     

Brain MRI findings in long-standing and disabling multiple sclerosis in 84 patients

Objective

To look for cerebral white matter MRI changes in patients with long-standing and disabling MS.

Methods

We analyzed retrospectively brain MRIs (performed 10 or more years after symptom onset) of patients with MS diagnosis and expanded disability status scale of 6 or more. The following parameters were analyzed: total number of brain T2 hyperintensities; number of brainstem, cerebellar, corpus callosum, basal ganglia, and juxtacortical T2 hyperintensities; diffuse leukoencephalopathy score; total number of T1 hypointensities.

Results

Eighty-four patients were included. The mean time between symptom onset and MRI was 20.2 years. Eight percent had less than 9 cerebral T2 hyperintensities. Posterior fossa, juxtacortical, and corpus callosum T2 hyperintensities, and T1 hypointensities lacked in respectively 19%, 12%, 47%, and 8%. Overall, normal MRI was not seen, 6% had abnormal MRI but did not meet Barkhof's criteria, and the remaining 94% had MRI abnormalities fulfilling Barkhof's criteria. Moderate or severe diffuse leukoencephalopathy was seen in 69%. Extensive diffuse leukoencephalopathy predominant to nodular lesions was seen in 5%.

Conclusions

Despite long-standing and disabling MS, typical MRI abnormalities lacked in a minority of patients, and 6% did not fulfil Barkhof's criteria. The majority showed moderate or severe diffuse leukoencephalopathy.     

Morphometry of myelin fibers in corpus callosum and optic nerve of aging rats.

Results of morphometric studies are presented, conducted on myelin fibers of corpus callosum and optic nerve of old rats. The studies were performed on 2 and 2.5 years old rats of Wistar strain. The control group consisted of 4 months old animals. The measurements were conducted on electron micrographs taken at magnification of 35,000 X. Aging was associated with increased thickness of myelin sheaths resulting both from increased number of myelin lamellae and from increased interlamellae distances (i.e. decreased compactness of myelin). The increased transversal size of myelin fibers, analogous to that observed in human material, was particularly evident in 2 years old rats. In the oldest, 2.5 years old rats size of myelin fibers decreased compared to 2 years old rats, approaching values observed in the control group. Moreover, disturbances in axon-myelin sheath ratio took place in the course od aging of rat brain white matter; axon cross-section area ratio to number of myelin lamellae in corpus callosum fibers was decreased while it was increased in fibers of optic nerve in 2 years old animals. In the process of aging most pronounced alterations were noted in thin fibers but thick fibers became more numerous and showed greater number of myelin lamellae.     

Early paranodal myelin swellings (tomacula) in an avian riboflavin deficiency model of demyelinating neuropathy

Introduction

Disruption of the complex architectural and molecular organization of the paranodal region of myelinated peripheral nerve fiber may initiate the evolving time dependent process of segmental demyelination. In support of this notion was the finding of focal paranodal myelin swellings (tomacula) due to redundant folding of myelin sheaths, early in the time course of an avian riboflavin deficiency model of demyelinating neuropathy.

Methods

Newborn broiler meat chickens were maintained either on a routine diet containing 5.0 mg/kg riboflavin (control group) or a riboflavin-deficient diet containing 1.8 mg/kg riboflavin. Riboflavin concentrations in the liver were measured at postnatal day 11. Peripheral nerves were morphologically examined at days 6, 11, 16 and 21 using light and electron microscopy and teased nerve fiber techniques.

Results

Riboflavin-deficient chickens showed signs of a neuropathy from days 8 and pathological examination of peripheral nerves revealed a demyelinating neuropathy with paranodal tomacula formation starting on day 11. Paranodal tomacula consisted of redundant myelin infoldings or outfoldings, increased in size and frequency after day 11. After day 16, the paranodal swellings showed prominent degenerative changes accompanied by an increased frequency of myelinated fibers showing demyelination.

Conclusion

Tomacula due to redundant myelin folds are generally considered a remyelination phenomenon, yet in this avian riboflavin deficiency model of demyelination, the paranodal tomacula occurred early in the course of demyelination.     

Paliperidone-associated motor tics

Objectives

Paliperidone-associated motor tics.

Method

Case report.

Results

We report a 30-year-old man with schizophrenia who developed motor tics (eye blinking) after treatment of paliperidone up to 15 mg daily.

Conclusion

Tic-like symptoms, from simple eye blinking to complex Tourette-like syndrome, may occur during paliperidone treatment, especially with high dose.     

Enfermedad de Parkinson avanzada. Características clínicas y tratamiento (parte I)

Introduction

A large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease.

Objective

To define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease.

Development

This consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL).

Conclusions

Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD.     

Interhemispheric approach to tumors of the posterior gyrus cinguli

Objective

Posterior gyrus cinguli tumors are a well-defined group of tumors that pose considerable challenges in creating surgical access and manipulating adjacent eloquent areas (visual and motor). Here we report our 5-year experience in the surgical treatment of these tumors and describe tumor characteristics, surgical steps, critical aspects, and prognostic factors.

Methods

This series comprises 37 patients operated on for glioma (high-grade in 28, low-grade in 9), often presenting with motor impairment (n = 20), intracranial hypertension (n = 15), seizures (n = 11), and/or hemianopia (n = 9). Preoperative assessment was performed with magnetic resonance imaging. Half of the tumors were more than 4 cm in size, and the majority presented secondary extension into the fronto-parieto-occipital area, the temporo-mesial area, and/or the corpus callosum. Positioning and assisted surgery were optimized in each patient based on preoperative planning.

Results

The ipsilateral interhemispheric approach was elected in all cases. Tumor size and extension were significantly associated with the degree of tumor removal. Total removal was achieved in 25 patients (65%); 4 (10%) had persistent morbidity (visual or motor deficits). The occurrence of local and systemic complications was negligible.

Conclusions

Surgical treatment of posterior gyrus cinguli tumors can be safely approached via the interhemispheric route as it permits several beneficial operative maneuvers in selected cases.     

Phrenic nerve studies predict survival in amyotrophic lateral sclerosis

Objective

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease associated with short survival due to respiratory failure. We aimed to test the predictive value of the phrenic nerve motor response for survival, in a large population of ALS patients.

Methods

We included 254 ALS patients followed in our tertiary centre from 1997 to 2006, in whom phrenic nerve stimulation was performed according to the study inclusion and exclusion criteria. ALS was spinal onset in 175 and bulbar onset in 79 patients. The following features were recorded at entry: gender, age at presentation, onset region, diagnostic delay, forced vital capacity (FVC), ALS functional rating scale (ALS-FRS) including the respiratory subscore of the reviewed ALS-FRS and mean amplitude of motor responses by phrenic nerve stimulation (PhrenAmpl).

Results

Survival analysis was evaluated by Kaplan–Meier log-rank test and multivariate Cox proportional hazards. Independent factors negatively affecting survival were bulbar onset, short diagnostic delay, FVC and small PhrenAmpl for the total population. Small PhrenAmpl and short diagnostic delay were also independent factors for both spinal and bulbar-onset patients; age at onset and FVC were also independent predictors in bulbar-onset patients.

Conclusion

Phrenic nerve stimulation is a non-volitional test that can be performed quickly in most patients; it is a powerful predictor of survival in ALS.

Significance

Phrenic nerve stimulation should be considered as an additional test for respiratory assessment in ALS.