[Traumatic homonymous hemianopsia and ganglion cell complex changes: Report of 3 cases]. / Hémianopsie latérale homonyme post-traumatique et atteinte des cellules ganglionnaires : à propos de 3 cas.

Homonymous lateral hemianopia follows an attack on the contralateral retrochiasmal visual pathways. In three patients with post-traumatic homonymous hemianopia, optical coherence tomographic (OCT) study of the ganglion cell layer thickness showed hemiretinal thinning contralateral to the visual field defect. This involvement could be explained by trans-synaptic degeneration of the pre-geniculate visual pathways, whose cell nuclei correspond to ganglion cells, which synapse with the damaged retrogeniculate visual pathways.

Retrograde Degeneration of Retinal Ganglion Cells Secondary to Head Trauma.

PURPOSE: To discuss the clinical case of a patient with transsynaptic retrograde degeneration (TRD) demonstrated by progressive retinal nerve fiber layer loss documented by serial spectral domain optical coherence tomography secondary to traumatic brain injury after 2 months post-trauma. CASE REPORT: A 25-year-old Caucasian male patient presented to a polytrauma rehabilitation center (PRC) for evaluation and treatment secondary to a severe traumatic brain injury (TBI) from a motorcycle accident 2 months before. Spectral-domain optical coherence tomography (SD-OCT) was completed at intervals that ranged between 8 and 42 days for a duration of 119 days. A comparison to the pre-trauma SD-OCT 10 months before revealed progressive thinning of the retinal nerve fiber layer (RNFL) in both eyes over multiple follow-ups post-trauma. Humphrey visual field (HVF) testing revealed an incomplete congruous right homonymous hemianopsia that gradually improved over the follow-ups. Analysis of the macular ganglion cell-inner plexiform layer (GCIPL) thickness displayed loss that corresponded to the pattern of visual field defect. CONCLUSIONS: TRD can occur as soon as 2 months after severe TBI with damage posterior to the lateral geniculate nucleus. Progressive RNFL loss can be tracked with SD-OCT, and the rate of thinning may slowly stabilize over time. Visual field defects can improve months after the trauma but may not correspond to the progressive RNFL loss detected by SD-OCT.

Longitudinal evidence for anterograde trans-synaptic degeneration after optic neuritis.

In multiple sclerosis, microstructural damage of normal-appearing brain tissue is an important feature of its pathology. Understanding these mechanisms is vital to help develop neuroprotective strategies. The visual pathway is a key model to study mechanisms of damage and recovery in demyelination. Anterograde trans-synaptic degeneration across the lateral geniculate nuclei has been suggested as a mechanism of tissue damage to explain optic radiation abnormalities seen in association with demyelinating disease and optic neuritis, although evidence for this has relied solely on cross-sectional studies. We therefore aimed to assess: (i) longitudinal changes in the diffusion properties of optic radiations after optic neuritis suggesting trans-synaptic degeneration; (ii) the predictive value of early optic nerve magnetic resonance imaging measures for late optic radiations changes; and (iii) the impact on visual outcome of both optic nerve and brain post-optic neuritis changes. Twenty-eight consecutive patients with acute optic neuritis and eight healthy controls were assessed visually (logMAR, colour vision, and Sloan 1.25%, 5%, 25%) and by magnetic resonance imaging, at baseline, 3, 6, and 12 months. Magnetic resonance imaging sequences performed (and metrics obtained) were: (i) optic nerve fluid-attenuated inversion-recovery (optic nerve cross-sectional area); (ii) optic nerve proton density fast spin-echo (optic nerve proton density-lesion length); (iii) optic nerve post-gadolinium T1-weighted (Gd-enhanced lesion length); and (iv) brain diffusion-weighted imaging (to derive optic radiation fractional anisotropy, radial diffusivity, and axial diffusivity). Mixed-effects and multivariate regression models were performed, adjusting for age, gender, and optic radiation lesion load. These identified changes over time and associations between early optic nerve measures and 1-year global optic radiation/clinical measures. The fractional anisotropy in patients' optic radiations decreased (P = 0.018) and radial diffusivity increased (P = 0.002) over 1 year following optic neuritis, whereas optic radiation measures were unchanged in controls. Also, smaller cross-sectional areas of affected optic nerves at 3 months post-optic neuritis predicted lower fractional anisotropy and higher radial diffusivity at 1 year (P = 0.007) in the optic radiations, whereas none of the inflammatory measures of the optic nerve predicted changes in optic radiations. Finally, greater Gd-enhanced lesion length at baseline and greater optic nerve proton density-lesion length at 1 year were associated with worse visual function at 1 year (P = 0.034 for both). Neither the cross-sectional area of the affected optic nerve after optic neuritis nor the damage in optic radiations was associated with 1-year visual outcome. Our longitudinal study shows that, after optic neuritis, there is progressive damage to the optic radiations, greater in patients with early residual optic nerve atrophy, even after adjusting for optic radiation lesions. These findings provide evidence for trans-synaptic degeneration.

Evaluation of retinal nerve fiber layer thickness measured by optical coherence tomography in Moroccan patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by focal inflammatory infiltrates, demyelinating lesions and axonal injury. The purpose of the study was to evaluate the retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in Moroccan patients with MS and to assess the relationship between RNFL thickness and disease duration, Expanded Disability Status Scale (EDSS) score, visual acuity and automated visual field indices. MATERIALS AND METHODS: Thirty-one patients with definite MS and thirty-one disease-free controls were enrolled in the study. After neurologic consultation, ophthalmologic examination including visual acuity, automated visual field testing and OCT were performed. RESULTS: Significant differences between both groups were observed in OCT parameters (total, temporal and macular ganglion cell layer) with lower thickness in the MS group. In patients without a history of optic neuritis, there were statistically significant inverse correlations between total RNFL thickness and disease duration, neurologic disability evaluated by the EDSS, logMAR visual acuity and automated visual field indices. CONCLUSIONS: OCT seems to be a reproducible test to detect axonal loss of ganglion cells in MS. Further and larger longitudinal prospective studies would be valuable to assess the evolution over time of the RNFL measurements in Moroccan MS patients.

Transsynaptic retinal degeneration in optic neuropathies: optical coherence tomography study.

PURPOSE: Recently demonstrated neuronal loss in the inner nuclear layer of the retina in multiple sclerosis (MS) and glaucoma raises the question of a primary (possibly immune-mediated) or secondary (transsynaptic) mechanism of retinal damage in these diseases. In the present study we used optical coherence tomography to investigate retrograde retinal transsynaptic degeneration in patients with long-standing and severe loss of ganglion cells due to optic neuropathy. METHODS: Fifteen eyes of glaucoma patients with visual field defect limited to upper hemifield and 15 eyes of MS patients with previous episode of optic neuritis (ON) and extensive loss of ganglion cells were imaged using spectral-domain optical coherence tomography and compared with two groups of age-matched controls. Combined retinal ganglion cell layer/inner plexiform layer (GCL/IPL) thickness and inner nuclear layer (INL) thickness were analyzed. RESULTS: In the glaucoma group there was a significant (P = 0.0005) reduction of GCL/IPL thickness in the lower (affected) retina compared with normal controls; however INL thickness was not statistically reduced (P = 0.49). In the MS group reduction of GCL/IPL thickness in both hemifields of ON eyes was also significant (P = 0.0001 and P < 0.0001 for inferior and superior retina respectively). However, similar to the glaucomatous eyes, there was no significant reduction of INL thickness in both hemifields (P = 0.25 and P = 0.45). CONCLUSIONS: This study demonstrates no significant loss of INL thickness in parts of the retina with long-standing and severe loss of retinal ganglion cells.

Acquired retrograde transsynaptic degeneration.

Although retrograde transsynaptic degeneration in the visual pathway of monkeys has been described since 1963, data in humans are sparse. The authors present a 24-year-old female referred to a neuro-ophthalmology consult for assessment before neurosurgery for a right occipital ependymoma. Clinical examination was unremarkable, including visual fields evaluated by computerised static perimetry. Four years after tumour extraction, the patient showed a left homonymous haemianopia documented by computerised static perimetry and a bow-tie like atrophy on the left on funduscopy. MRI revealed right occipital cortex lobectomy and optic tract atrophy. The presence of left homonymous haemianopia, the characteristic pattern of optic disc atrophy and right optic tract atrophy 4 years after right occipital tumour excision, strongly suggest the presence of retrograde transsynaptic degeneration. To our knowledge, this is the first time that retrograde transsynaptic degeneration-associated optic tract atrophy is clearly demonstrated by MRI.

In vivo imaging of retinal ganglion cell axons within the nerve fiber layer.

Purpose. Optic nerve injury causes loss of retinal ganglion cells (RGCs) and their axons. The reduction in RGC counts over time in axonal injury is well studied, but the correlation with the timing of anterograde and retrograde axonal degeneration is less clear. The authors longitudinally imaged RGC axons stained with a chloromethyl derivative of fluorescein diacetate (CMFDA) in live rats after optic nerve injury. Methods. Optic nerves were transected. Three days later CMFDA was intravitreously injected. Confocal scanning laser ophthalmoscopy was performed daily, and mean fluorescence intensity and the number of CMFDA bundles were calculated. RGC soma survival was studied after retrograde fluorescence labeling. Retinal nerve fiber layer (RNFL) thickness was evaluated histologically. Results. CMFDA-positive RGC axon bundles could be imaged in vivo. Axons lost 68% +/- 29% of their fluorescence by 7 days after transection compared with 25% +/- 21% in nontransected eyes. The number of labeled axon bundles decreased by 61% +/- 28% at 7 days after transection compared with 26% +/- 9% in nontransected eyes. The number of retrograde-labeled RGCs detected in vivo declined by 53% at 7 days and by 76% at 14 days after transection. RGC soma and CMFDA axon counts decreased most rapidly between 5 and 7 days after transection. Histologic examination demonstrated a reduction in RNFL thickness 7 days after transection. Conclusions. Intravitreal CMFDA can be used to longitudinally monitor RGC axons within the RNFL in vivo. Imaging the disappearance of retrograde-labeled RGC somas and axons indicates that axonal and somal degeneration occur in parallel after axotomy.

Retrograde trans-synaptic retinal ganglion cell loss identified by optical coherence tomography.

There is experimental evidence of trans-synaptic retrograde degeneration of retinal ganglion cells following retrogeniculate visual pathway lesions in primate studies. Retinal nerve fibre loss in congenital homonymous hemianopia in humans is well recognized from clinical observation but the findings in acquired lesions have been controversial. Forty-eight persons were recruited and divided into three groups. Two groups were patients with retrogeniculate lesions. In the first group, the occipital damage had occurred during childhood or in adult life whilst the lesions in the second group were congenital. Inclusion criteria for the retrogeniculate lesions included: age >18 years at time of testing; homonymous hemianopia; no other ophthalmic or neurological disorder; and neuroimaging demonstration of occipital lobe damage. The third group had normal visual function. Measurement of the thickness of the peripapillary retinal nerve fibre layer by optical coherence tomography has been carried out in both eyes of each subject. The primary outcome is the peripapillary retinal nerve fibre layer thickness (RNT) in microns. The mean RNT in the eyes with temporal hemianopia (here called the 'crossing-fibre defect' eyes) is 79.8 mu (SD = 35.1 mu) in the acquired and 72.7 mu (SD = 33.2 mu) in the congenital. The mean RNT in eyes with nasal hemianopia (here called the 'non-crossing-fibre defect' eyes) is 83 mu (SD = 29.5 mu) in the acquired and 73.4 mu (SD = 26 mu) in the congenital. In the control group, the RNT measured 101.4 mu (SD = 36.6 mu) for the left eyes and 100.8 mu (SD = 35.4 mu) for the right eyes. In both crossing-fibre defect eyes and non-crossing-fibre defect eyes the mean RNT is significantly greater in the controls than in the hemianopia groups (P < 0.001). These data confirm that there is thinning of the retinal nerve fibre layer following both congenital and acquired lesions of the retrogeniculate visual pathway in humans. This is most likely to represent retinal ganglion cell loss in both congential and acquired groups. Furthermore the magnitude of the thinning is similar in both groups despite the fact that clinical observation has consistently found evidence of RNT thinning in cases of congenital but not in cases of acquired pathology. The data have also been analysed in 12 sectors around the optic disc: it has been shown that the RNT thinning follows the known trajectories of the crossing and non-crossing retinal ganglion cell axons approaching the disc.

[What is a peripheral neuropathy?]. / Qu'est-ce qu'une neuropathie périphérique?

Peripheral neuropathies may be classified according to the localisation of symptoms and signs. This step necessitates a good knowledge of the peripheral nervous system anatomy. The diagnostic strategy relies on this classification and allows, thanks to the neurophysiological exam to establish the pathogenic mechanism of the neuropathy. These data are important to limit the possible aetiologies to a reasonable number in order to use the appropriate paraclinical work-up. Laboratory examinations may be simple or sophisticated and their use may require the help of an expert center. In a limited number of cases, nerve biopsy is still a very useful tool to determinate the mechanism of peripheral neuropathy and to guide the treatment.

Sympathetic skin response and axon count in carpal tunnel syndrome.

The aim of this study was to determine the sensitivity of sympathetic skin response (SSR) in evaluating autonomic involvement in carpal tunnel syndrome (CTS) while simultaneously showing the axonal loss by motor unit number estimation (MUNE). Bilateral SSR were recorded by suprasternal stimulus in 50 hands of 31 patients and compared with 50 hands of 25 healthy volunteers. The groups were examined for sympathetic symptoms and sympathetic symptom scores (SSS) were determined. Axon count was performed on the abductor pollicis brevis (APB) muscle by using the MUNE method (with incremental technique) in both groups. There was no SSR difference between groups, although a significant difference was found for SSS. No relationships were found between SSR parameters and SSS or the electrophysiologic stage. MUNE of the APB muscle was significantly lower in CTS group and there was a negative correlation between MUNE and the electrophysiologic stage. The comparison of the MUNE and the amplitude of median compound muscle action potential indicated that MUNE is a highly sensitive method of determining severity in patients with CTS. In evaluating autonomic involvement in CTS, SSR does not seem to be a sensitive method. MUNE is a good indicator of motor reserve and can be helpful when following the treatment and prognosis of CTS in clinical practice.

Optic nerve atrophy and retinal nerve fibre layer thinning following optic neuritis: evidence that axonal loss is a substrate of MRI-detected atrophy.

Magnetic resonance imaging (MRI) measures of brain atrophy are often considered to be a marker of axonal loss in multiple sclerosis (MS) but evidence is limited. Optic neuritis is a common manifestation of MS and results in optic nerve atrophy. Retinal nerve fibre layer (RNFL) imaging is a non-invasive way of detecting axonal loss following optic neuritis. We hypothesise that if the optic nerve atrophy that develops following optic neuritis is contributed to by axonal loss, it will correlate with thinning of the RNFL. Twenty-five patients were studied at least 1 year after a single unilateral attack of optic neuritis without recurrence, with a selection bias towards incomplete recovery. They had MR quantification of optic nerve cross-sectional area and optic nerve lesion length, as well as optical coherence tomography (OCT) measurement of mean RNFL thickness and macular volume, quantitative visual testing, and visual evoked potentials (VEPs). Fifteen controls were also studied. Significant optic nerve atrophy (mean decrease 30% versus controls), RNFL thinning (mean decrease 33% versus controls), and macular volume loss occurred in patients' affected eyes when compared with patients' unaffected eyes and healthy controls. The optic nerve atrophy was correlated with the RNFL thinning, macular volume loss, visual acuity, visual field mean deviation, and whole field VEP amplitude but not latency. These findings suggest that axonal loss contributes to optic nerve atrophy following a single attack of optic neuritis. By inference, axonal loss due to other post-inflammatory brain lesions is likely to contribute to the global MRI measure of brain atrophy in multiple sclerosis.

Hereditary neuropathy with liability to pressure palsy: fulminant development with axonal loss during military training.

Hereditary neuropathy with liability to pressure palsy (HNPP) is characterised by recurrent mononeuropathies following minor trauma. We describe a case of fulminant HNPP beginning on the first day of military physical training. Protracted weakness, muscle atrophy, hand contractures, and multifocal sensory loss developed during a further three weeks of basic training. Nerve conduction changes were typical of HNPP, but without segmental slowing. Electromyographically, there was prominent acute denervation in muscles of the hands and right shoulder. Sural nerve biopsy demonstrated tomaculae and remyelination. Genetic testing revealed PMP-22 gene deletion. This case report demonstrates that HNPP can present with rapidly progressive peripheral nerve dysfunction and electrophysiological evidence of focal axonal loss.

Mycoplasma pneumoniae causing nervous system lesion and SIADH in the absence of pneumonia.

A patient was admitted for fever and acute respiratory failure (ARF), rapidly progressive tetraparesis, delirium, behavioral abnormalities, and diplopia. Leukocytosis and a rise in C-reactive protein were present. A syndrome of inappropriate anti-diuretic hormone secretion (SIADH) was also diagnosed. Lumbar puncture yielded colorless CFS with mononuclear pleocytosis and protein rise. Electrodiagnosis revealed demyelinating polyneuropathy and axonal degeneration. Serum IgG and IgM for mycoplasma pneumoniae (MP) was consistent with acute infection, and erythromycin was started with rapid resolution of symptoms. Contrarily to most reports, an associated respiratory disease was not present and SIADH in association with MP has been reported only once, in a patient without direct central nervous system (CNS) involvement. Differential diagnosis and possible pathogenic mechanisms are discussed.

Forearm mixed nerve conduction velocity: questionable role in the evaluation of retrograde axonal atrophy in carpal tunnel syndrome.

The objective of this study was to determine whether forearm mixed nerve conduction velocity (Fmix) reflects the real conduction velocity of forearm motor nerve (Fmot) and forearm sensory nerve (Fsen) fibers passing through the carpal tunnel. Forearm mixed nerve conduction velocity is presumed to be indicative of the conduction velocity of the median nerve over the forearm. Therefore, Fmix is used widely to assess the causes of slowing forearm conduction velocity in carpal tunnel syndrome. However, some authors claim that Fmix comes chiefly from the undamaged fibers in carpal tunnel syndrome, and thus cannot replace Fmot or Fsen in the evaluation of retrograde axonal atrophy. Patients with clinical symptoms and signs of carpal tunnel syndrome confirmed with standard electrodiagnosis were included. Age-matched volunteers served as control subjects. Conduction velocities across the wrist and over the forearm were measured, including those of the wrist sensory (Wsen), wrist motor (Wmot), and wrist mixed nerves (Wmix); and forearm mixed (Fmix), forearm motor (Fmot), and forearm sensory nerves (Fsen). The authors compared and correlated Wsen, Wmot, and Wmix; and Fmix, Fmot, and Fsen respectively. The mean values of Wsen, Wmot, Wmix, Fmix, Fmot, and Fsen of the control subjects less those of corresponding conduction velocity of carpal tunnel syndrome patients were designated Wsen N, Wmot N, Wmix N, Fmix N, Fmot N, and Fsen N respectively and were compared and correlated again. Wrist motor nerve conduction velocity, Wsen, and Wmix were significantly lower in carpal tunnel syndrome patients, and Fmot and Fsen but not Fmix were reduced significantly when compared with control subjects. Mean wrist sensory nerve conduction velocity, Wmot N, and Wmix N; and Fsen N and Fmot N showed good correlation except for Fmix N, suggesting that Fmix reflects the conduction velocity of undamaged fibers in carpal tunnel syndrome. Forearm mixed nerve conduction velocity cannot replace Fmot or Fsen in the assessment of retrograde axonal atrophy in carpal tunnel syndrome. In the disease state, Fmix possibly represents the conduction velocity of the palmar cutaneous branch.

Transneuronal degeneration in patients with temporal lobe epilepsy: evaluation by MR imaging.

The aim of this study was to assess the MR imaging findings of transneuronal degeneration of limbic system in the patients with temporal lobe epilepsy, and to detect the influence of surgery on the anatomy of the limbic system. Axial and coronal T1- and T2-weighted MR images were retrospectively analyzed in 34 patients with temporal lobe epilepsy, focusing on transneuronal degeneration. In 17 of the 34 patients, MR images were also analyzed after selective amygdalo-hippocampectomy. Atrophy of the fornix, mamillary body, mamillothalamic tract (MTT), and thalamus ipsilateral to the epileptic focus was demonstrated on MR images in 14.7, 17.6, 8.8, and 11.8% of the 34 patients, respectively. Focal hyperintensity of the thalamus was found on T2-weighted images in 8.8% of the 34 patients. In 17 patients who were evaluated before and after surgery, transneuronal degeneration was seen more frequently after surgery: fornix (11.8 vs 29.4%), mamillary body (11.8 vs 52.9%), MTT (5.9 vs 11.8%), and thalamus (11.8 vs 11.8%). Transneuronal degeneration of the limbic system is clearly demonstrated by MR imaging in patients with temporal lobe epilepsy, and surgical intervention induces transneuronal degeneration more frequently.

Inherited neuropathies.

Inherited neuropathies are common and are usually caused by mutations in genes that are expressed by myelinating Schwann cells or neurons, which is the biological basis for long-standing distinction between primary demyelinating and axonal neuropathies. Neuropathies can be isolated, the primary manifestation of a more complex syndrome, or overshadowed by other aspects of the inherited disease. Increasing knowledge of the molecular-genetic causes of inherited neuropathies facilitates faster, more accurate diagnosis, and sets the stage for development of specific therapeutic interventions.

Hereditary spastic paraplegia.

The hereditary spastic paraplegias are a large group of clinically similar disorders. Seventeen different HSP loci have been discovered thus far. Different genetic forms of uncomplicated HSP are clinically very similar. Except for the average age at which symptoms appear, different genetic types of uncomplicated HSP cannot be distinguished reliably by clinical parameters alone. For most subjects, HSP is a diagnosis of exclusion. The differential diagnosis includes treatable disorders as well as those for which the prognosis is quite different from HSP. Even with the emerging availability of laboratory testing for HSP gene mutations, it is still essential that alternative disorders be excluded by careful history, examination, laboratory studies, neuroimaging, and neurophysiologic evaluation. Uncomplicated HSP is due to axonal degeneration at the ends of the longest motor (corticospinal tract) and sensory (dorsal column fibers) in the spinal cord. The observation that some forms begin in childhood and are essentially nonprogressive while other forms begin in adulthood and are slowly progressive raises the possibility that some forms of HSP (e.g.; those associated with LICAM gene mutations and possibly those due to SPG3A mutations) are neurodevelopmental disorders; and other forms are truly neurodegenerative disorders. The mechanisms by which spastin, atlastin, and paraplegin mutations cause axonal degeneration that results in clinically similar forms of HSP are not known. Nonetheless, the identification of these genes and the ability to generate animal models of these forms of HSP will permit direct exploration of the molecular basis of HSP.