Magnetic Resonance Characteristics of Baló Concentric Sclerosis in Children.

BACKGROUND: Baló concentric sclerosis is a rare demyelinating disease with characteristic magnetic resonance appearance of multilayered ringlike lesions of demyelination. This disease is extremely rare in children. We present the clinical data, radiological appearance, and development of lesions in eight children. METHODS: We analyzed the clinical information of eight patients diagnosed between 2012 and 2020. Magnetic resonance brain and spinal cord examinations with contrast medium administration were performed using a 1.5-T scanner. RESULTS: All patients presented at least one typical Baló lesion on brain imaging. Four patients additionally had typical multiple sclerosis plaques. All primary Baló lesions had a characteristic appearance of concentric hyperintense rings on T2-weighted imaging and were round or ovoid. Cerebrospinal fluid analysis was performed in all patients. Oligoclonal bands were present in seven patients, and four of them had multiple sclerosis plaques on baseline brain magnetic resonance imaging. CONCLUSION: Baló concentric sclerosis in children is characterized by acute and severe onset with hemiparesis as a predominant symptom. The size, contrast enhancement, and restricted diffusion depend on the phase of the disease.

From Baló's concentric sclerosis to multiple sclerosis: a series of 6 patients.

INTRODUCTION: Baló's concentric sclerosis (BCS) is a rare CNS disorder characterized by alternating bands of demyelination on MRI. One of the main issues is its relationship with multiple sclerosis (MS). OBJECTIVES: To describe 6 BCS patients. To review the risk of developing MS in BCS patients. METHODS: We retrospectively recorded clinical and radiological findings of 6 BCS patients and performed a review of the literature. RESULTS: Six patients (5 women) with a mean age of 25 years old were included. Main symptoms were hemiparesis/hemihypoesthesia. On MRI, two patients had a single BCS lesion and four had additional MS-like lesions. Alternating bands were usually more visible on DWI. A patient had reduced central perfusion and SWI hypointensity suggestive of a central vein. Oligoclonal bands were identified in 5/6 patients. After 7 years of follow-up, all patients achieved MS criteria with mild disability (mean EDSS 1.75; 0-4). Our literature review included 65 BCS patients from 30 studies: although CSF oligoclonal bands and the presence of additional MS lesions were associated with subsequent relapses, this was not significant. DISCUSSION/CONCLUSION: Our series allows a detailed MRI description in BCS and gives a new insight into BCS evolution and its strong relationship with MS.

Myelinoclastic diffuse sclerosis (Schilder's disease) is immunologically distinct from multiple sclerosis: results from retrospective analysis of 92 lumbar punctures.

BACKGROUND: Myelinoclastic diffuse sclerosis (MDS; also termed Schilder's disease) is a rare inflammatory demyelinating disorder of the central nervous system characterised by demyelination of vast areas of the white matter. It is unclear whether MDS is a variant of multiple sclerosis (MS) or a disease entity in its own right. OBJECTIVE: To compare the cerebrospinal fluid (CSF) features of MDS with those of MS. METHODS: Retrospective analysis of the CSF profile of all patients with MDS reported in the medical literature between 1960 and 2018. RESULTS: The most striking finding was a substantial lack of oligoclonal bands (OCBs) in MDS, which were absent in at least 77% (30/39) of all lumbar punctures (LP) in the total cohort and in 86% in the subgroup of patients with normal very long-chain fatty acid serum ratios (VLCFA). Almost all cases published in the past 15 years were negative for OCBs. These findings are in contrast to MS, in which OCBs are present in up to 98% of cases (p < 0.00001 when compared with reference works in MS; both in adult and in pediatric patients). CSF pleocytosis was absent in at least 79% (46/58) of all LP (p < 0.0001 vs. MS) and in 92% (24/26) of LPs in the VLCFA-tested subgroup. CSF total protein levels were elevated in 56% of all LPs (p < 0.0001 vs. MS) and in 63% of LPs in the VLCFA-tested subgroup and were often higher than in typical MS (> 100 mg/dL in 13/22; up to 220 mg/dL). EBV serum antibodies, which are present in virtually all patients with MS, and the so-called MRZ (measles/rubella/zoster) reaction, a highly specific marker of MS, were absent in all of the few patients tested. In addition, we discuss further differences between MS and MDS, taking into account also Schilder's original comprehensive case description from 1912. CONCLUSION: In the majority of patients diagnosed with MDS, CSF features differ significantly from those typically found in MS and are more similar to those previously reported in patients with myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-positive encephalomyelitis, aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders or Baló's concentric sclerosis. Our data suggest that MDS and MS are immunopathologically distinct entities in the majority of cases.

[Clinical and biochemical characteristics of atypical variants of multiple sclerosis]. / Kliniko-biokhimicheskie kharakteristiki atipichnykh variantov rasseiannogo skleroza.

AIM: To study the clinical and biochemical features of atypical variants of multiple sclerosis (MS) (tumefactive demyelination (TD), Balo's concentric sclerosis (BCS)) and acute disseminated encephalomyelitis (ADEM)). MATERIAL AND METHODS: Forty-two patients were studied, including 32 patients with atypical variants of MS (6 patients with BCS and 26 patients with TD) and 10 patients with ADEM. The control group included 20 healthy volunteers. Clinical characteristics and EDSS scores were evaluated. Antibodies to aquaporin 1 (AQP1-IgG), aquaporin 4 (AQP4-IgG), antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) and aquaporin 1 (AQP1) in serum and cerebrospinal fluid (CSF) were detected using ELISA. RESULTS AND CONCLUSION: BCS and TD occurred both in isolation and comorbid with MS (in 50% of cases with BCS, 50% of cases with TD). Atypical symptoms of MS were detected in 50% of cases of CFS, 15.4% of cases of PD. The levels of CSF cytosis and CSF protein were not significantly different between the groups. The levels of AQP1-IgG, AQP4-IgG, AQP1, MOG-IgG in serum with BCS, TD and ADEM were significantly higher than in the control group. No significant differences were found between atypical variants of MS. A correlation between a high level of MOG-IgG and the EDSS score in BCS was shown. MOG-IgG may have a pathogenetic significance in BCS. Further studies of AQP1-IgG, AQP4-IgG and MOG-IgG in patients with atypical variants of MS are needed.

Baló's concentric sclerosis is immunologically distinct from multiple sclerosis: results from retrospective analysis of almost 150 lumbar punctures.

BACKGROUND: Baló's concentric sclerosis (BCS) is a rare inflammatory demyelinating disorder of the central nervous system characterised by concentric layers of demyelination. It is unclear whether BCS is a variant of multiple sclerosis (MS) or a disease entity in its own right. OBJECTIVE: To compare the cerebrospinal fluid (CSF) features of BCS to those of MS. METHODS: Retrospective analysis of the CSF profile of all patients with BCS reported in the medical literature between 1980 and 2017. RESULTS: In total, the results of 146 lumbar punctures (LP) in 132 patients were analysed. The most striking finding was a lack of CSF-restricted oligoclonal bands (OCB) in 66% (56/85) of all LP in the total BCS group, in 74% (14/19) in the subgroup of patients with both MRI and histological evidence for BCS, and in 82% (18/22) in the subgroup of patients with highest radiological confidence (high MRI quality, ≥ 3 layers of demyelination). OCB disappeared in 1/2 initially OCB-positive patients. These findings are in stark contrast to MS, in which OCB are present in ≥ 95% of patients and are thought to remain stably detectable over the entire course of disease (p < 0.000001). OCB frequency was low both in 'historic' patients (1980-2009; 37%) and in more recent patients (2010-2017; 31%). OCB-positive and OCB-negative patients did not differ significantly with regard to age, sex, disease duration, number of Baló-like lesions on MRI, number of relapses, treatment or final outcome. In accordance with the high rate of OCB negativity, Link's IgG index was negative in 63% of all tested samples (p < 0.000001 vs. MS). CSF pleocytosis was present in 28% (27/96; p < 0.000001 vs. MS) and elevated CSF total protein levels in 41% (31/76) of samples. CONCLUSION: OCB and IgG index frequencies in BCS are much more similar to those reported in neuromyelitis optica or myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis than to those in MS. Our findings suggest that in most cases BCS-like lesions denote the presence of a disease entity immunologically distinct from MS. In addition, we provide data on the demographics, clinical course and radiological features of BCS based on the largest cohort analysed to date.

Cerebral folate deficiency and CNS inflammatory markers in Alpers disease.

We describe a 3.5-year-old female with Alpers disease with a POLG genotype of p.A467T/p.G848S and with a lethal outcome. Laboratory investigation revealed elevated CSF neopterin, IL-6, IL-8, IFN-gamma, reduced CSF 5-methyltetrahydrofolate (5MTHF), and increased serum as well as CSF folate receptor blocking autoantibodies. Treatment with oral Leucovorine (5-formyl-tetrahydrofolate) was initiated at 0.25mg/kg bid, and later increased to 4mg/kg bid. Under treatment CSF levels of 5MTHF, seizure frequency and communicative abilities improved. Over a time span of 17months, CSF levels of IL-6 and IFN-gamma decreased, levels of folate receptor blocking autoantibodies continued to raise, whereas CSF IL-8 remained elevated 1500-fold above normal. The child died without apparent stress at the age of 5.5years. Alpers disease, a neurodegenerative disease usually presents in the first years of life as a progressive encephalopathy with multifocal myoclonic seizures, developmental regression, cortical blindness and early death. The underlying genetic defect has been attributed to mutations of the catalytic subunit of the mitochondrial DNA polymerase-gamma leading to an organ-specific mitochondrial DNA depletion syndrome with reduced activity of respiratory chain enzyme complexes in the brain and the liver. A curative therapy is not available. This case report of Alpers disease provides new insights into the pathophysiology of Alpers disease, where mitochondrial dysfunction in conjunction with inflammatory cytokines and blocking folate receptor autoantibodies may lead to a secondary cerebral folate deficiency syndrome. The treatment of the latter provides relief to the patient without stopping the underlying disease.

Acquired demyelinating disorders of childhood in the Western Cape, South Africa.

In a retrospective review of patients with acquired demyelinating disorders of the central nervous system, 19 children (0.6%) were identified from the Paediatric Neurology database of 3159 patients; 7 had acute disseminated encephalomyelitis, 1 had Schilder's disease, 5 had multiple sclerosis, and 6 had acute transverse myelitis. The median age of presentation was 83 months, with increased incidence during the summer and winter months. The commonest presentation was hemiparesis. The commonest regions of magnetic resonance imaging (MRI) abnormalities were the deep white matter (68%) and cerebellum (48%).The patients with multiple sclerosis had more monosymptomatic presentations (P < .02), raised cerebrospinal fluid protein (P = .022), and contrast enhancement of lesions (P = .05) compared with the acute disseminated encephalomyelitis group. Neuroepidemiological published surveillances of African children provide no data about these disorders. The prevalence of acquired demyelinating disorders in resource-poor settings is under-estimated because of the large burden of infections and limited access to neuroimaging.

[Baló's concentric sclerosis: lesions restricted to the pons]. / Sclérose concentrique de Baló: lésions uniquement pontines.

A clinico-pathological case of Baló's concentric sclerosis is reported. Besides the rarity of the disease, this case was interesting because of the late onset of the illness (50 years) the normality of the CSF and the localization of the lesions which were restricted to the pons.

Gamma-aminobutyric acid-transaminase deficiency: a newly recognized inborn error of neurotransmitter metabolism.

Cerebrospinal fluid aminoacid analysis in a girl with severe psychomotor retardation, hypotonia, hyperreflexia and growth acceleration showed highly increased levels of free gamma-aminobutyric acid (4.8 mumol/l; range in twenty controls 0.04-0.12, median 0.08), homocarnosine, a dipeptide of gamma-aminobutyric acid and histidine (23.4 mumol/l; control range 4.0-8.7, median 7.6) and of beta-alanine, an alternative substrate for gamma-aminobutyric acid-transaminase (0.48 mumol/l; control range 0.02-0.06, median 0.05). Liver gamma-aminobutyric acid-transaminase activity was deficient (0.07 mumol/mg protein h; range in ten controls 0.31-0.69, median 0.38). Fasting plasma growth hormone levels were increased (7.9-38.4 ng/ml; nl less than 5). Brain evoked responses were suggestive of leukodystrophy. A brother of this patient, showing a similar clinical picture, had died at one year. Postmortem examination of his brain showed leukodystrophy of the type seen in amino acidopathies such as phenylketonuria. This appears to be the first report of gamma-aminobutyric acid-transaminase deficiency.

[Baló's concentric sclerosis]. / Sclérose concentrique de Baló.

A clinico-pathological case of concentric sclerosis (Baló type) is reported. A 30-year-old man experienced dizziness, nausea and vomiting. Twelve days later he developed gait disturbances. Neurological examination showed broad based gait, brisk tendon reflexes, bilateral extensor plantar responses, right hemihypoesthesia, cerebellar dysmetria, and a left lateral gaze palsy. CSF examination showed, 520 mg p. 100 ml protein, 7500 red blood cells, 31 lymphocytes and 9 polymorphonuclear leukocytes/mm3, 18 p. 100 gammaglobulin. Three CT scans were performed and showed a round hypodensity in the parieto-occipital white matter with contrast enhancement on one occasion, and several other hypodensities in the contralateral parieto-occipital white matter and in both frontal lobes. 23 days after the onset of the disease, the patient became comatose. A cerebral biopsy was obtained from one of the frontal lesions. He died from aspiration bronchopneumonia 2 months after the first signs. Neuropathological examination showed numerous concentric zones of demyelination which involved the white matter of both hemispheres, brain stem, and cerebellum. On light microscopy sudanophilic myelin breakdown products were numerous in the bands of demyelinisation. Astrocytic proliferation was marked, with frequent Rosenthal fibers. Edema was noted in some lesions. Myelin-axonal dissociation was obvious, but some axonal swelling were observed. Electron microscopy demonstrated the integrity of oligodendrocytes and of blood vessels and confirmed the prominent alterations of the astrocytes. Fifteen similar cases of the literature have been reviewed. The present case seems to be the first one with CT scan examination and electron microscopic study of a brain biopsy. The nosological situation of Baló's disease among the inflammatory demyelinating diseases of the group of MS is discussed.

[Measurements of the intracranial CSF spaces by computer tomography (author's transl)]. / Quantifizierung der intrakraniellen Liquorräume durch die Computertomographie.

A method for quantifying the CSF compartments in cranial computer tomograms is described. The method is based on an analysis of the histogram curve, the proportion of area and thickness of the liquor spaces being related to the total area below the curve. In order to isolate the skull contents, a CT masking technique is used. The practicability and usefulness of the method in clinical practice was tested in 59 normal patients and in eleven patients with rapidly progressing brain atrophy.

[Necrotic aspects of multiple sclerosis and Schilder's disease (author's transl)]. / Les formes cavitaires de la sclérose en plaques et de la maladie de Schilder.

Two anatomo-clinical cases of a necrotic form of demyelinating disease are reported. The disease occurred in two women, had a late onset (patient were about 50 years old) and had a relapsing-remitting course during more than 10 years. The CSF displayed a high protein level over 125 mg/100 ml whereas the gamma-globulin level was normal. The anatomical study found symmetrical cavitations involving both hemispheres and optic tracts with clear-cut limits. Axons and myelin were both destroyed, only the vascular network being partially spared. At the lesion's border-line mononuclear cell infiltrates as well as some phagocytes with sudanophilic inclusions were found. The scarcity of the compound granular corpuscules suggest an old pathological process. A narrow zone of myelin-axonal dissociation was also observed. Astrocytic proliferations was unimportant. Blood vessels were normal. In one case plaques of multiple sclerosis were found in the spinal cord. Those two cases are unusual forms of a diffuse disseminated sclerosis: multiple sclerosis and Schilder's disease are considered as two anatomo-clinical variants of the same pathological process. The observed necrotic lesions are different from the acute necrotic forms of multiple sclerosis as the latter have rapidly developed. The long lasting course of the disease, over 10 years, allowed a complete resolution of the lesions explaining the cavitations. The late onset of the disease and the CSF high protein level are pointed out. The significant of the high protein level and normal gammaglobulin level in the CSF is discussed.

Adrenoleukodystrophy. Report of two cases with relapsing and remitting courses.

Two boys with adrenoleukodystrophy (ALD) had unusual clinical courses. The first had three episodes of relapse and two remissions associated with elevation and fall in CSF protein levels. The second boy has had a prolonged remission of his neurologic symptoms with continuing adrenocortical failure. There may be a limited role for steroids in the treatment of the cerebral aspects of ALD.

Computed tomographic evaluation of the early phase of adrenoleukodystrophy.

Analysis of computed tomograms of patients with adrenoleukodystrophy in the early disease phase reveals a dinstinct CT apperance. It is suggested that brain or adrenal biopsy may not be necessary for diagnosis of adrenoleukodystrophy when these particular CT features are correlated with the clinical course and other laboratory parameters.

Lymphocyte subpopulations in human cerebrospinal fluid.

Lymphocyte subpopulations in both human cerebrospinal fluid and peripheral blood were identified and compared by rosette techniques. In patients without neuroaxial disease, the percent distribution of Fc receptor and T-lymphocytes reflected peripheral blood values, although there was a significantly higher percentage of T cells in normal CSF. Alterations in lymphocyte cerebrospinal fluid populations were observed in various systemic and neurologic diseases.

[Cerebrospinal fluid phospholipids and cerebrosides in several demyelinating diseases]. / Fosfolipidy i tserebrozidy likvora pri nekotorykh demieliniziruiushchikh zabolevaniiakh

The author reports of the achieved results in a quantitative study of general lipids, phospholipids and cerebrosides in the CSF of 37 patients with demyelinating diseases, of 11 patients with vascular brain pathology and 7 with Van Bogart's panencephalitis. The control group consisted of 14 patients without focal lesions of the nervous system, with normal CSF indices. In demyelinating diseases there was a significant increase in the content of kephalines and cerebrosides. In Van Bogart's panencephalitis there was a much higher increase of kephalines, general lipids and phospholipids. In vascular brain disorders there was a moderate increase of all lipids. The possible pathochemical mechanisms of the depicted changes in the content of the lipids in the CSF are discussed.

Barrier impairment and immune reaction in the cerebrospinal fluid.

Investigations on pathophysiological processes in the CSF space due to impairment of the blood-CSF barrier and due to an immune reaction are reported. Barrier disturbances and immune reaction are demonstrated by means of absolute values of CSF protein electrophoresis and by measurement of immunoglobulins. With inflammatory diseases of the CNS, an altered blood-CSF barrier will often be seen at the moment of the first lumbar puncture. Multiple sclerosis, subacute leucoencephalitis and neurosyphilis show signs of a distinct immune reaction together with an increase of the gamma-globulins as well as the immunoglobulin G in the absence or slight presence of a barrier impairment. Non-inflammatory diseases of the CNS have variable barrier disturbances.