Lipid analysis in nerve biopsy specimens of hypertrophic neuropathy.

We performed a lipid analysis on nerve biopsy specimens in two cases of degenerative hypertrophic neuropathy. Quantitative analysis of the major lipid classes, ie, cholesterol, cerebrosides, sulfatides, ethanolamine phospholipids, phosphatidyl-choline, phosphatidyl-serine, phosphatidyl-inositol, sphingomyelin, and gangliosides, were performed. The two cases exhibited extreme decreases in levels of lipids that could be related to the very low myelin content of these nerves. Cholesterol and phospholipid levels were especially reduced. Cerebrosides and sulfatides were not modified in the same proportion, as could have been predicted from the degree of demyelination. This relative glycolipid increase could be due to the very high Schwann cell proliferation.

Metachromatic leukodystrophy. Ultrastructural and enzymatic study of a case of variant O form.

A variant of metachromatic leukodystrophy (MLD), Austin disease, is characterized by a multiple isozyme deficiency of arylsulfatase. A 3 1/2-year-old girl with progressive mental and physical deterioration had decreased activities of arylsulfatases A and B in the leukocytes, shown by acylamide gel electrophoresis. Under the electron microscope, biopsy specimens of the brain and the peripheral nerve showed lamellar structures with socalled zebra bodies in the cytoplasmic processes of glial cells, granulo-membranous inclusions with fingerprint configurations in neurons, and myelinlike material in Schwann cells. Results from our study suggest an intricate nature of this dysmetabolic disorder, which shows ultrastructural changes usually seen in classic MLD, a deficiency of arylsulfatase A only, concomitant with those seen in mucopolysaccharidoses such as Hurler and Sanfilippo syndromes.

Value of multiple sclerosis diagnostic criteria. 70 autopsy-confirmed cases.

We have evaluated the sensitivity of the most recent and most frequently used criteria for the diagnosis of definite multiple sclerosis by the retrospective study of the clinical files of 70 pathologically confirmed cases. For each case, the date of diagnosis was determined separately using different sets of criteria. The delay of diagnosis was then calculated. The diagnosis was made significantly earlier when certain criteria were used. This was more marked in the earlier years of the disease. We also found that cases of multiple sclerosis with progressive courses were diagnosed later than cases with other courses, whatever the criteria used. This was statistically significant only for a single criterion.

Peroneal muscular atrophy. Part 2. Nerve biopsy studies.

The present study used the nerve pathology, studied by quantitative light microscopy, as the sole basis for classification of peroneal muscular atrophy (PMA). The findings in biopsies of superficial peroneal nerves of 20 patients were compared with normal values obtained from 8 controls. Three homogeneous groups comprising 17 out of 20 patients were clearly identified. The hypertrophic type (7 cases) was characterized by (1) many multilamellated onion bulb formations; (2) extensive loss of MF with both involvement of the largest and smallest fibers; (3) lack of significant cluster formation. The neuronal sensori-motor type (5 cases) was characterized by (1) absence of any OB; (2) elective loss of large MF; (3) abundance of clusters with significant increase of the small MF population. The neuronal motor type (5 cases) showed a virtually normal sensory nerve except for fairly numerous clusters in some cases. Comparing this classification based on histomorphometric grounds, with the electrophysiological data it appears that 14 patients out of 17 would be correctly classified as hypertrophic or neuronal with respect to the motor nerve conduction velocity of the median nerve alone. Three cases were not classified in the previous groups since they differed notably in one or more parameters from the typical cases. A possible intermediate group is discussed.

Bulbar infarcts. Vascular lesions in 26 observations. / Les infarctus bulbaires. Etude des lésions vasculaires dans 26 observations.

The pattern of arterial occlusion and related lesions have been studied in 26 cases with 38 medullary infarcts. In 10 of these cases, only the intracranial vessels were examined. In the 16 other cases, the entire cerebral arterial supply was dissected. Medial infarcts were more often related to occlusion of the vertebral artery involving the termination of the artery (7/10 cases). In 6 cases a thrombosis on an atheromatous plaque and, once, an embolus of cardiac origin, were found. Lateral infarcts were usually due either to occlusion of the vertebral artery (14/23 cases), reaching, in 10 cases, the mouth of the posterior inferior cerebellar artery (PICA) or to an isolated occlusion of the latter vessel (3 cases). A thrombosis on an atheromatous plaque was found in 15 cases, and emboli from the heart or from the origin of the vertebral artery in the others. The dorsal infarcts were related, in 4/5 cases, to an isolated occlusion of the stem of the PICA and, in the other case, to one of the vertebral artery involving the ostium of the PICA. A thrombosis due to atheromatous stenosis was found in 4 cases, an embolus of cardiac origin in the other one.

Bulbar infarcts. Systematic study of lesion topography in 49 cases. / Les infarctus bulbaires. Etude systématique de la topographie lésionnelle dans 49 cas.

A pathological study has been carried out of 49 examples of medullary infarction in 33 patients. The medial infarcts, very seldom single (2 /12), spared the subolivary levels. The pontomedullary junction was affected in 3 /9 cases studied. The lesions were more frequent in the ventral part of the arterial zonal pattern. They more often extended to its dorsal part at the level of the middle and upper one-third of the olive. The lateral infarcts, seldom single (6/30), extended to the subolivary levels in 6/22 cases studied and to the pontomedullary junction in 9/24 cases. The structures involved in each case and the area of the lesions at each cranio-caudal level have been studied. None of the 7 dorsal infarcts was single; in 6 of these cases there was also a cerebellar infarct involving the area of supply of the posterior inferior cerebellar artery. The subolivary levels (1/6) and ponto-medullary junctions (1/6) were seldom affected. The extent of the lesions in these uncommon infarcts has been described in detail.

Analysis of the major lipid classes in human peripheral nerve biopsies. Age group differences and abnormalities of ganglioside level in perhexiline maleate therapy.

We report here the results of a simple and reproducible technique which can be used in semi-routine analysis of peripheral nerve biopsy specimens, so as to have a quantitative analysis of the major lipid classes, i.e. cholesterol, cerebrosides, ethanolamine phospholipids, phosphatidyl-choline, phosphatidyl-serine + phosphatidylinositol, sphingomyelin and gangliosides. Glycolipid hexoses, cholesterol and total phospholipids have been compared in different age groups. Although all lipid classes increased from the younger to the older age group, the molar ratio of cholesterol to phospholipid differed less than the glycolipid to phospholipid ratio. Both increased significantly, even between age group 10--16 and older patients (36, 54, 61, 68, 72 and 73 years old). Although individual variations in lipid content are noteworthy, it must be emphasized that evolution with age of the lipid composition must be taken into account. Furthermore, this study confirms and extends earlier findings of increased ganglioside levels in some cases of peripheral neuropathies observed during perhexiline maleate therapy where characteristic lipid-like polymorphous inclusions have been demonstrated.

Postmortem studies on posthypoxic and post-methyl bromide intoxication: case reports.

In two cases of action myoclonus following hypoxic or shock encephalopathy, neuropathological examination disclosed mild or moderate scattered changes involving thalamus, griseum centrale mesencephali, and nucleus centralis superior. Other areas were affected only in one of these cases (striatum, nucleus subthalamicus or hippocampus, nuclei pontis, and cerebellar cortex). In another case (an alcoholic patient), the changes, which involved only corpus mamillare and thalamus, were those of Wernicke-Korsakoff encephalopathy. In one case of oscillatory myoclonus following septic shock, there were marked cerebellar changes involving deep nuclei and mild abnormalities in the thalamus and inferior olive. The last case of action myoclonus following acute methyl bromide intoxication was characterized by marked changes in the inferior colliculi and moderate or mild abnormalities of thalamus, griseum centrale mesencephali, nucleus centralis superior, nucleus reticularis tegmenti pontis, nuclei pontis, and dentatus. The findings are compared with the data of seven previously reported neuropathological examinations in action myoclonus following hypoxic encephalopathy.

[Steele-Richardson-Olszewski disease without ophthalmoplegia. 6 clinico-anatomic cases]. / Maladie de Steele-Richardson-Olszewski sans ophtalmoplégie. Six cas anatomo-cliniques.

Six clinico-pathological cases (4 males and 2 females) with a Parkinson-like syndrome which lasted an average of 5 1/2 years are reported. The average age at death was 73 years. Neuropathological features were similar to those described in post encephalitic Parkinson's syndrome and in Steele-Richardson-Olszewski disease. However, neurofibrillary tangles were less numerous; lesions in tectal, periaqueductal and reticular structures were less severe. Furthermore, the lesions seemed more pronounced in the substantia nigra, the globus pallidus and the nucleus subthalamicus, giving the appearance of a systematic pallido-luyso-nigral atrophy. None of these patients had a history of encephalitis. Clinical examination did not reveal the dystonic rigidity in extension of the neck nor the characteristic ophthalmoplegia of progressive supranuclear palsy. These 6 cases are compared to 10 cases of progressive supranuclear palsy typical both on clinical and pathological grounds. They could be considered as a particular form of Steele-Richardson-Olszewski disease without ophthalmoplegia.

[318 cases of intracerebral hemorrhage. A pathologic study (author's transl)]. / Etude anatomique de 318 hémorragies intra-parenchymateuses de l'adulte.

The systemic analysis of cerebral hemorrhages (large single and multiple hematomas and small slit-hemorrhages) has been practiced in 318 patients. The emphasis is put on the site of the bleeding and the etiological data. Single hematomas were situated: 1) in 127 cases in the basal ganglia region (26 were medial, 44 intermediate, 48 lateral, 8 quadrilateral and one subthalamic), 2) in 67 cases in cerebral lobes (24: front; 22: temporal; 21 parietal) and 3) in 33 cases in the posterior fossa (19: cerebellum; 14: brain stem). Large hematomas in 71 cases and slit-hemorrhages in 20 others were multiple. In more than one case out of three, lateral hematomas extended into the temporal lobe and in one case out of two, the internal capsule was affected. The incidence of high blood pressure is significantly higher in patients with intermediate haematomas and slit hemorrhages. This factor is often found in lateral or cerebellar hematomas. Anticoagulant therapy is more frequent in lobar hematomas. In 43 cases without any proved etiology, the patients' mean age of death is inferior to that of the whole studied population. These findings are discussed in relation with the literature data.

[Arteriopathic leukoencephalopathy (17 anatomo-clinical cases)]. / Leucoencéphalopathies artériopathiques. (17 cas anatomo-cliniques).

Seventeen clinico-pathological cases of leukoencephalopathy due to vascular diseases are reported. All of them had diffuse, often spotty demyelination sparing the U fibers, the corpus callosum, the internal capsule and the optic radiations. Microscopic examination of the white matter showed the association of the following lesions: oedema, swollen oligodendroglia, spongiosis, incomplete loss of myelin, astrocytic gliosis with Rosenthal's fibers, widening of the perivascular spaces with oedema fluid or hemosiderin laden macrophages, thickening and hyalinization of the blood vessels walls. Among those cases, 8 were consistent with Binswanger's subcortical encephalopathy (5 males, 3 females, mean age at death: 64 years, mean illness duration: 6, 7 years); all of them were hypertensive and had lacunae in the basal ganglia, hemispheric white matter and pons. Another case could be considered as a cortico-subcortical chronic hypertensive encephalopathy (77 y.o., female, illness duration: 4 years); she was hypertensive and had small cortical infarcts and perivascular bleedings, lobar and cerebellar hematomas, but no amyloid deposits in the blood vessels walls. Eight patients (5 males, 3 females mean age at death: 72 years, mean illness duration: 5, 4 years, 6 normotensive, 2 hypertensive) had diffuse meningocortical amyloid angiopathy with multiple small cortical infarcts, small cortical perivascular bleedings, slit haemorrhages and one or more lobar hematomas. Four of them had numerous senile plaques and neurofibrillary tangles. To our knowledge such a leukoencephalopathy in cerebral amyloid angiopathy has not been yet pointed out. It was present in 8 out of 12 cases of diffuse haemorrhagic form of cerebral amyloid angiopathy observed in the Charles Foix Laboratory of la Salpêtrière, during the last 10 years. A common mechanism with hypoperfusion of the distal white matter and alteration of the blood brain-barrier is suggested for this leukoencephalopathy.

[Cerebellar atrophies]. / Les atrophies cérébelleuses.

The concept of cerebellar atrophy was first introduced by Pierre Marie in 1893 in his description of hereditary cerebellar ataxia. Subsequent criticism of this notion was refuted by the report of new clinicopathological entities which are compatible with it. The contributions of the Clinic for Diseases of the Nervous System are discussed in this paper. Etiological classification is difficult, in spite of progress made in the genetic, epidemiologic, and biochemical approaches to cerebellar atrophies. Pathologic findings appear to supply the most secure basis for presentation of these affections. Predominantly cortical atrophies may be localized to the vermis. This is the case in the familial cerebello-olivary atrophy of Holmes (1907), in tardive cortical atrophy (Pierre Marie, Foix and Alajouanine, 1922), and in the cerebellar atrophy of alcoholics (Alajouanine, Castaigne, Contamin and Lebourges, 1959; Victor, Adams and Mancall, 1959), in which the lesions are similar. The frequent intrication of the various etiological factors: age, deficiencies, alcohol, heredity, suggests the role of a sometimes primary, sometimes latent genetic predisposition, revealed during various pathological conditions. Cortical cerebellar atrophy may be of the diffuse type, as in paraneoplastic cerebellar atrophy (Brouwer and Biemond, 1938), which is closely related to subacute polioencephalomyelitis in cancer patients (Dubas et al., 1982), and in congenital atrophy of the granular layer (Norman, 1940), which is more a dysgenesis than a true degenerative affection. Lesions affecting mainly the efferent or afferent cerebellar pathways include olivopontocerebellar atrophy (Dejerine and André Thomas, 1900) which should be included in the larger overall concept of multiple system atrophy (Oppenheimer, 1976), and dentorubric atrophy (Ramsay Hunt, 1921) which themselves should be integrated in the group of spinocerebellar atrophies. Finally, olivorubrocerebellar atrophy (Lejonne and Lhermitte, 1909) and crossed cerebellar atrophy, traditionally studied together with cerebellar atrophies, are only the result of a pre-existing lesion.

[Catecholaminergic axons in the human cerebral cortex. Observation by histofluorescence of cerebral biopsies in 2 cases of Alzheimer's disease]. / Axones catécholaminergiques du cortex cérébral humain. Observation, en histofluorescence, de biopsies cérébrales dont 2 cas de maladie d'Alzheimer

Catecholamine axons have been visualized in human cerebral cortex obtained during routine neurosurgical operations. The fluorescence histochemical method of Lindvall et al. was used, slightly modified (calcium-deprived buffer, glyoxylic acid fixation followed by formaldehyde vapours exposition). The frontal cortex was more richely provided with catecholamine terminals than the parietal cortex. Two general types of axon morphology are evident. The most frequent is thin and sinous, sometimes forming clews, or loose basket-like arrangement around presumed nerve cells. The other one is moniliform and demonstrates spherical evenly-spaced varicosities. They look like, respectively, the well characterized dopaminergic and noradrenergic axons of the rat cerebral cortex. In two cases of Alzheimer's disease, noradrenergic-like fibers were missing and voluminous green-fluorescent varicosities, sometimes in obvious connection with typical axons, were observed in the proximity of senile plaques.

[Huntington's chorea and cerebellar atrophy. Apropos of amanatomo-clinical case]. / Chorée de Huntington et atrophie cérébelleuse. (A propos d'une observation anatomo-clinique)

The authors report the clinical and pathological findings in a 46 years old woman with Huntington's chorea and cerebello-olivar atrophy. Eight previously reported cerebellar atrophies in Huntington's chorea with pathological examination are reviewed. The primary or secondary nature of the cerebellar lesions is discussed.

[Akinetic mutism and bicingular softening. 3 anatomo-clinical cases]. / "Mutisme akinétique" et ramollissement bicingulaire. 3. observations anatomo-cliniques

The authors describe three pathological cases of akinetic mutism with, as a common basic lesion, bilateral infarction of the cingulate gyrus secondary to aneurysm of the anterior communicating artery (case n degrees 1), to a huge olfactory meningioma (case n degrees 2), both operated on, and to atheromatous occlusion of the anterior cerebral arterial system (case n degrees 3). These three cases enable a variety of "anterior and waking" akinetic mutism to be described which is unusual enough to be compared with other mesencephalic and diencephalic aspects of this syndrome. It is in fact an akinetic mutism characterized by: a certain dissociation in its non-response to various stimuli, a particularly marked appearance of wakefulness when day-time alertness is considered, conservation of the waking-sleeping rhythm, perception and reaction unpredictable and paradoxical in both degree and quality, complete absence of any spontaneous verbal communication in contrast to relative break-down of solicited communication which is infrequent, uncertain and unresponsive to the usual methods of stimulation, without any possibility of a code. In addition, there is a remarkable mimic and segmental general akinesia, resistant to the usual nociceptive stimuli, but sensitive to slight excitation of the manual and oral zones. Besides this special akinetic mutism, there are variously systematised signs, mostly asymmetrical, indicating lesion of the cortico-sub-cortical frontal structures bordering on the gyrus cinguli. This unusual behaviour pattern corresponds in these three cases to extensive anterior bilateral ischemic lesions of the cingulate gyrus regularly associated with bilateral infarctions confined to the medial aspect of F1 in the superficial territory of the two anterior cerebral arteries, to possible neurosurgical changes (ablation of the right frontal pole) and to compressive or ischaemic lesions of the gyrus rectus. These exclusively cortico-sub-cortical associated lesions are in contrast with the remarkably intact caudate nuclei, the pallidal, thalamic, hypothalamic and septal formations and the anterior pillars of the fornix. These findings compared with the results of experimental research carried out by M. Kennard, help, if help is needed, to resolve the apparent contradictions between the effects of therapeutic cingulectomies or cingulotomies and the scanty pathological data already available in cerebral vascular pathology.

[Strümpell Lorrain's familial spasmodic paraplegia. An anatomical and clinical review and report on a new case (author's transl)]. / La paraplégie spasmodique familiale de Strümpell-Lorrain (P.S.F.). Une nouvelle observation anatomo-clinique.

The authors describe the anatomical and clinical findings in a case of the pure form of Strümpell Lorrain's familial spasmodic paraplegia. This hereditary condition of the dominant autosomic type has very monomorphic pathognomonic features which are found in all patients affected. The slowly progressive isolated spastic hypertonia appears exclusively in the upright position and the extent of the disease can be ascertained by clinical observation during walking. The myelino-axial degeneration which is strictly limited to the spinal cord has an elective localization in the crossed pyramidal tracts, is less evident in the direct tracts and is mainly predominant in the lumbosacral and low dorsal regions of the cord. The extension of the process beyond the limits of the extrapyramidal tracts confirms the generally accepted unity of spinocerebellar degenerations. In this case the spinocerebellar tracts were less involved than the lumbar spinal ganglia, as well as their distant axial continuation to Goll's tracts only at the cervical level and until the bulber nucleus gracilis.

[Quantitative study of the peripheral nerve in semi-thin section by the Nomarski interference contrast technic]. / Etude quantitative du nerf pêriphêrique sur coupes semi-fines par la technique du contraste interfêrentiel de Nomarski

The Normarski interference-contrast microscope is well suited to observations of transverse thick sections of epon-embedded peripheral nerves. The quantitative study of myelinated fibers is possible on photomicrographs with a final magnification of X 500. The induced distorsion is very small as compared with the results obtained by conventional bright field and positive phase contrast optics. The comparative study of the same field with the three devices allows a better interpretation of marginal pictures.

[Parinaud's syndrome and tonic vertical gaze deviation. 3 anatomo-clinical observations]. / Syndrome de Parinaud et déviation tonique verticale du regard. Trois observations anatomo-cliniques.

Two anatomo-clinical cases of downward gaze palsy and one case of upward gaze palsy are reported. A tonic and intermittent downward gaze deviation is described. The supranuclear palsies of the downward gaze were related to paramedian lesions of the rostral mesencephalon; the lesions involved the rostral interstitial nucleus of the medial longitudinal fasciculus, the nucleus interstitial of Cajal, and/or their afferent and/or efferent pathways. The supranuclear palsy of the upward gaze was related to lesions of the posterior commissure. Tonic and intermittent downward deviation of gaze and ocular bobbing have opposed features. The former could be related to disinhibited reticular mesencephalic neurones activated by vestibular inputs. Tonic upward deviation of gaze is also related to a vestibulo-ocular reflex. In this case, partial or total damage of the nucleus of Cajal, and/or its input and/or its output fibers appears to have a critical role.

[Cavitary orthochromatic leukodystrophy in the adult. Oligodendroglial proliferation and inclusions]. / Leucodystrophie orthochromatique cavitaire de l'adulte. Prolifération et inclusions oligodendrogliales.

A 41 year-old woman presented with two Grand Mal fits followed by progressive spastic paraparesis and intellectual impairment. After 18 months there was a remission which lasted for 4 years but thereafter inexorable progression of the disease and many fits led to a state of akinetic mutism. Death occurred nine and a half years after the onset of the illness. There was no family history. The neuropathological studies included light and electron microscopy of a cerebral biopsy and a complete post mortem examination. Myelin loss and cavitation of the white matter was associated with the presence of sudanophilic lipid and abundant cells at the periphery of the lesions. These cells had the characteristics of oligodendrocytes. The combination of sudanophilic leucodystrophy, cavitation of white matter and oligodendrocyte proliferation has previously been observed only in childhood.

[Motor neglect of thalamic origin: report on two cases (author's transl)]. / La négligence motrice d'origine thalamique. A propos de deux cas.

Two cases of thalamic lesions with motor neglect are presented. The syndrome of motor neglect was complete in those cases with a) underutilization of left limbs, but good utilization upon verbal orders, b) loss of placement reaction, c) weakness of movement when hand was approaching the target, d) weakness of motor reaction to nociceptive stimuli. Those cases confirm that motor neglect exists after thalamic lesions and bring pathologic clues for topographic discussion. Motor neglect seems to be a particular case of partial unilateral neglect throwing some doubt on the hypothesis of a global trouble of hemispheric activation. Prevalence of left motor neglects suggests some linkage between propositional motility and language. One may suppose that in the right hemisphere language is able to have a vicarious action when spontaneous activation is lost; at the opposite, in the left hemisphere language and motility would be too linked to let this dissociation be generally possible.