Acute amnestic syndrome is an uncommon clinical presentation of neurological disease. Differential diagnosis encompasses several syndromes including Wernicke-Korsakoff and transient global amnesia ...(TGA). Structural lesions of the fornix account for a minority of cases of acute amnestic syndromes. Etiology varies from iatrogenic injury to ischemic, inflammatory, or neoplastic lesions. A prompt diagnosis of the underlying pathology is essential but challenging. The aim of this review is to systematically review the existing literature regarding cases of acute amnestic syndrome associated with non-iatrogenic lesions of the fornix.
We performed a systematic literature search on PubMed, Scopus, and Web of Science up to September 2023 to identify case reports and case series of patients with amnestic syndrome due to fornix lesions. The systematic review was conducted according to PRISMA guidelines. The research was limited to articles written in English. Cases of fornix damage directly ascribable to a surgical procedure were excluded.
A total of 52 publications reporting 55 cases were included in the review. Focusing on acute/subacute onset, vascular etiology was highly prevalent, being responsible for 78% of cases, 40/55 (74%) of which were due to acute ischemic stroke. The amnestic syndrome was characterized by anterograde amnesia in all patients, associated with retrograde amnesia in 27% of cases. Amnesia was an isolated presentation in most cases. Up to two thirds of patients had persistent memory deficits of any severity at follow-up.
Acute amnestic syndrome can be rarely caused by fornix lesions. In most cases of acute/subacute presentation, the etiology is ischemic stroke, mainly caused by strokes involving the subcallosal artery territory. The differential diagnosis is challenging and a distinction from common mimics is often difficult on a clinical basis. A high index of suspicion should be maintained to avoid misdiagnosis and provide adequate acute treatment to patients with time-dependent disease, also employing advanced neuroimaging. More research is needed to better understand the outcome and identify prognostic factors in patients with amnestic syndrome due to fornix lesions.
Abstract Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical ...features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center study. In 20 patients (65%) CCPD presented, after an infection, as myeloradiculoneuropathy, encephalopathy, cranial neuropathy, length-dependent peripheral neuropathy, or pseudo-Guillain-Barré syndrome. Demyelinating features of peripheral nerve damage fulfilling European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria for CIDP were found in 23 patients (74%), and brain MRI lesions fulfilling the 2010 McDonald criteria for multiple sclerosis (MS) in 11 (46%). Two thirds of the patients had a relapsing or progressive disease course, usually related to the appearance of new spinal cord lesions or worsening of the peripheral neuropathy, and showed unsatisfactory responses to high-dose corticosteroids and intravenous immunoglobulins. The clinical presentation of CCPD was severe in 22 patients (71%), who were left significantly disabled. Our data suggest that CCPD has heterogeneous features and shows frequent post-infectious onset, primary peripheral nervous system or central nervous system involvement, a monophasic or chronic disease course, inadequate response to treatments, and a generally poor outcome. We therefore conclude that the current diagnostic criteria for MS and CIDP may not fully encompass the spectrum of possible manifestations of CCPD, whose pathogenesis remains largely unknown.
In this work, we develop a kinetic model of tumour growth taking into account the effects of clinical uncertainties characterising the tumours’ progression. The action of therapeutic protocols trying ...to steer the tumours’ volume towards a target size is then investigated by means of suitable selective-type controls acting at the level of cellular dynamics. By means of classical tools of statistical mechanics for many-agent systems, we are able to prove that it is possible to dampen clinical uncertainties across the scales. To take into account the scarcity of clinical data and the possible source of error in the image segmentation of tumours’ evolution, we estimated empirical distributions of relevant parameters that are considered to calibrate the resulting model obtained from real cases of primary glioblastoma. Suitable numerical methods for uncertainty quantification of the resulting kinetic equations are discussed and, in the last part of the paper, we compare the effectiveness of the introduced control approaches in reducing the variability in tumours’ size due to the presence of uncertain quantities.
•New kinetic model for tumour growth with clinical uncertainties.•The action of therapeutic protocols steers the tumours’ volume towards a target size.•The introduced therapies reduce the variability due to uncertain quantities.•Calibration of the model based on MRI scans.•Examples based on UQ methods for kinetic equations.
Background and purpose
Mutations in the small heat‐shock protein 22 gene (HSPB8) have been associated with Charcot‐Marie‐Tooth disease type 2L, distal hereditary motor neuropathy (dHMN) type IIa and, ...more recently, distal myopathy/myofibrillar myopathy (MFM) with protein aggregates and TDP‐43 inclusions. The aim was to report a novel family with HSPB8K141E‐related dHMN/MFM and to investigate, in a patient muscle biopsy, whether the presence of protein aggregates was paralleled by altered TDP‐43 function.
Methods
We reviewed clinical and genetic data. We assessed TDP‐43 expression by qPCR and alternative splicing of four previously validated direct TDP‐43 target exons in four genes by reverse transcriptase–polymerase chain reaction.
Results
The triplets and their mother presented in the second to third decade of life with progressive weakness affecting distal and proximal lower limb and truncal muscles. Nerve conduction study showed a motor axonal neuropathy. The clinical features, moderately raised creatin kinase levels, selective pattern of muscle involvement on magnetic resonance imaging and pathological changes on muscle biopsy, including the presence of protein aggregates, supported the diagnosis of a contemporary primary muscle involvement. In affected muscle tissue we observed a consistent alteration of TDP‐43‐dependent splicing in three out of four TDP‐43‐target transcripts (POLDIP3, FNIP1 and BRD8), as well as a significant decrease of TDP‐43 mRNA levels.
Conclusions
Our study confirmed the role of mutated HSPB8 as a cause of a combined neuromuscular disorder encompassing dHMN and MFM with protein aggregates. We identified impaired RNA metabolism, secondary to TDP‐43 loss of function, as a possible pathological mechanism of HSPB8K141E toxicity, leading to muscle and nerve degeneration.
Background: Several authors have used advanced magnetic resonance imaging (MRI) techniques to investigate whether patients with neuromyelitis optica (NMO) have occult damage in normal-appearing brain ...tissue, similarly to multiple sclerosis (MS). To date, the literature contains no data derived from the combined use of several advanced MRI techniques in the same NMO subjects.
Objective: We set out to determine whether occult damage could be detected in the normal-appearing brain tissue of a small group of patients with NMO using a multiparametric MRI approach.
Methods: Eight female patients affected by NMO (age range 44–58 years) and seven sex- and age-matched healthy controls were included. The techniques used on a 1.5 T MRI imaging scanner were magnetization transfer imaging, diffusion tensor imaging, tract-based spatial statistics, spectroscopy and voxel-based morphometry in order to analyse normal-appearing white matter and normal-appearing grey matter.
Results: Structural and metabolic parameters showed no abnormalities in normal-appearing white matter of patients with NMO. Conversely, tract-based spatial statistics demonstrated a selective alteration of the optic pathways and the lateral geniculate nuclei. Diffusion tensor imaging values in the normal-appearing grey matter were found to be significantly different in the patients with NMO versus the healthy controls. Moreover, voxel-based morphometry analysis demonstrated a significant density and volume reduction of the sensorimotor cortex and the visual cortex.
Conclusions: Our data disclosed occult structural damage in the brain of patients with NMO, predominantly involving regions connected with motor and visual systems. This damage seems to be the direct consequence of transsynaptic degeneration triggered by lesions of the optic nerve and spine.
Background and purpose
Patients with a history of brain radiotherapy can experience acute stroke‐like syndromes related to the delayed effects of brain radiation, including stroke‐like migraine ...attacks after radiation therapy syndrome, peri‐ictal pseudoprogression and acute late‐onset encephalopathy after radiation therapy syndrome. The aim of this study was to collect evidence on the long‐term outcome and treatment of these conditions, whose knowledge is undermined by their rarity and fragmented description.
Methods
Cases were collected, both prospectively and retrospectively, amongst six neuro‐oncology departments. Inclusion criteria were as follows: (i) history of brain radiotherapy (completed at least 6 months before the acute episode); (ii) new onset of acute/subacute neurological symptoms; (iii) exclusion of all etiologies unrelated to brain irradiation. A review of current literature on stroke‐like syndromes was performed to corroborate our findings.
Results
Thirty‐two patients with acute neurological conditions attributed to the delayed effects of radiation were identified, including 26 patients with stroke‐like syndromes. Patients with stroke‐like syndromes commonly presented with a mosaic of symptoms, including focal deficits (77%), encephalopathy (50%), seizures (35%) and headache (35%). Seventy‐three percent of them had acute consistent magnetic resonance imaging alterations. Treatment included high‐dose steroids in 65% of cases. Twenty‐two patients recovered completely (85%). Sixteen patients (62%) experienced relapses (median follow‐up 3.5 years). A literature review identified 87 additional stroke‐like cases with similar characteristics.
Conclusions
Stroke‐like events related to brain irradiation may be associated with permanent sequelae. Steroids are often administered on empirical grounds, as they are thought to accelerate recovery. Relapses are common, highlighting the need to elaborate adequate prevention strategies.
To evaluate the usefulness of arterial spin labelling (ASL) qualitative analysis for the localisation of seizure-related perfusion abnormalities in paediatric patients with negative brain magnetic ...resonance imaging (MRI) epilepsy.
Forty-two patients with a diagnosis of MRI-negative focal or generalised epilepsy, who underwent electroencephalogram (EEG) and MRI with ASL in the interictal phase were included. Perfusion abnormalities were evaluated through a qualitative assessment and then compared to EEG seizure focus.
Among the 42 patients, 26 had focal epilepsy and 16 had generalised epilepsy. Thirty-three patients (79%) showed a perfusion abnormality, mainly hypoperfusion (74.5% of all ASL alterations), whereas hyperperfused alterations were more represented in patients who experienced the last seizure either less than 48 hours prior to ASL acquisition or in the time interval from 1 week to 1 month prior to ASL acquisition (p=0.034). Concordance of ASL abnormality and EEG focus was found in 33 patients (78.5%), as complete in 17 (40.5%) and as partial in 16 (38%). A trend of higher concordance was found in focal epilepsies compared to generalised epilepsies (p=0.059). The concordance between ASL and EEG major alterations was higher for hyperperfused anomalies than for hypoperfused ones (p=0.009). Variables such as age, sedation, and time from last seizure were not significant contributors for concordance.
The combined use of qualitative ASL and brain MRI and scalp EEG could be a potential tool in daily clinical practice.
•To evaluate ASL usefulness in identifying seizure-related perfusion abnormalities.•The majority of patients (79%) showed a perfusion abnormality, mainly hypoperfusion.•Concordance of ASL abnormality and EEG focus was found in 78% of patients.•Hyperperfused alterations showed better EEG concordance than hypoperfused ones.
Pompe disease is an autosomal recessive disorder in which deficiency of the lysosomal enzyme acid alpha-glucosidase results in the accumulation of glycogen mostly in muscle tissues. Several reports ...suggest a higher incidence of intracranial vascular abnormalities (IVAs) in this condition, as well as brain microbleeds and cerebral vasculopathy. The aim of our study was to evaluate through neuroimaging studies the incidence of these anomalies in our cohort of late-onset Pompe disease (LOPD) patients asymptomatic for cerebrovascular disease, looking for correlations with clinical and genetic data. We studied 18 LOPD patients with brain magnetic resonance angiography (MRA), or contrast-enhanced computed tomography (CECT). Diameters of individual arteries were measured and compared with average values as proposed in the literature. We found IVAs in 13 of the 18 patients, mostly dilatative arteriopathy affecting the vertebrobasilar system. The anterior circle was involved in seven of the 18 patients. The diameter of the basilar artery at 1 cm was found to correlate both with age (spearman rho,
p
= 0.037) and disease duration (
p
= 0.004), but no other statistically significant correlation was documented. The incidence of intracranial dilatative arteriopathy in LOPD was higher than in the general population, confirming the literature data. However, we did not find intracranial aneurysms microbleeds or significant cerebrovascular disease. Abnormalities in the anterior and the posterior circle of Willis correlated with age and disease duration, but not with the severity of muscle/respiratory involvement or with genetic data. Further studies in larger cohorts of patients are needed to confirm these findings.
Congenital muscular dystrophies (CMD) with reduced glycosylation of alpha-dystroglycan (alpha-DG) are a heterogeneous group of conditions associated with mutations in six genes encoding proven or ...putative glycosyltransferases.
The aim of the study was to establish the prevalence of mutations in the six genes in the Italian population and the spectrum of clinical and brain MRI findings.
As part of a multicentric study involving all the tertiary neuromuscular centers in Italy, FKRP, POMT1, POMT2, POMGnT1, fukutin, and LARGE were screened in 81 patients with CMD and alpha-DG reduction on muscle biopsy (n = 76) or with a phenotype suggestive of alpha-dystroglycanopathy but in whom a muscle biopsy was not available for alpha-DG immunostaining (n = 5).
Homozygous and compound heterozygous mutations were detected in a total of 43/81 patients (53%), and included seven novel variants. Mutations in POMT1 were the most prevalent in our cohort (21%), followed by POMT2 (11%), POMGnT1 (10%), and FKRP (9%). One patient carried two heterozygous mutations in fukutin and one case harbored a new homozygous variant in LARGE. No clear-cut genotype-phenotype correlation could be observed with each gene, resulting in a wide spectrum of clinical phenotypes. The more severe phenotypes, however, appeared to be consistently associated with mutations predicted to result in a severe disruption of the respective genes.
Our data broaden the clinical spectrum associated with mutations in glycosyltransferases and provide data on their prevalence in the Italian population.
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