Quantitative brainstem and spinal MRI in amyotrophic lateral sclerosis: implications for predicting noninvasive ventilation needs.

BACKGROUND: Respiratory complications resulting from motor neurons degeneration are the primary cause of death in amyotrophic lateral sclerosis (ALS). Predicting the need for non-invasive ventilation (NIV) in ALS is important for advance care planning and clinical trial design. The aim of this study was to assess the potential of quantitative MRI at the brainstem and spinal cord levels to predict the need for NIV during the first six months after diagnosis. METHODS: Forty-one ALS patients underwent MRI and spirometry shortly after diagnosis. The need for NIV was monitored according to French health guidelines for 6 months. The performance of four regression models based on: clinical variables, brainstem structures volumes, cervical spinal measurements, and combined variables were compared to predict the need for NIV within this period. RESULTS: Both the clinical model (R2 = 0.28, AUC = 0.85, AICc = 42.67, BIC = 49.8) and the brainstem structures' volumes model (R2 = 0.30, AUC = 0.85, AICc = 40.13, BIC = 46.99) demonstrated good predictive performance. In addition, cervical spinal cord measurements model similar performance (R2 = 0.338, AUC = 0.87, AICc = 37.99, BIC = 44.49). Notably, the combined model incorporating predictors from all three models yielded the best performance (R2 = 0.60, AUC = 0.959, AICc = 36.38, BIC = 44.8). These findings are supported by observed positive correlations between brainstem volumes, cervical (C4/C7) cross-sectional area, and spirometry-measured lung volumes. CONCLUSIONS: Our study shows that brainstem volumes and spinal cord area are promising measures to predict respiratory intervention needs in ALS.

Cannabis for the treatment of amyotrophic lateral sclerosis: What is the patients' view?

Cannabis may have therapeutic benefits to relieve symptoms of amyotrophic lateral sclerosis (ALS) thanks to its pleiotropic pharmacological activity. This study is the first to present a large questionnaire-based survey about the "real-life" situation regarding cannabis use in the medical context in ALS patients in France. There were 129 respondents and 28 reported the use of cannabis (21.7%) to relieve symptoms of ALS. Participants mostly reported the use of cannabidiol (CBD) oil and cannabis weed and declared benefits both on motor (rigidity, cramps, fasciculations) and non-motor (sleep quality, pain, emotional state, quality of life, depression) symptoms and only eight reported minor adverse reactions (drowsiness, euphoria and dry mouth). Even if cannabis is mostly used outside medical pathways and could expose patients to complications (street and uncontrolled drugs, drug-drug interactions, adverse effects…), most of the participants reported "rational" consumption (legal cannabinoids, with only few combustion and adverse reactions). Despite some limitations, this study highlights the need for further research on the potential benefits of cannabis use for the management of ALS motor and non-motor symptoms. Indeed, there is an urgent need and call for and from patients to know more about cannabis and secure its use in a medical context.

COVID-19-related encephalopathy: a case series with brain FDG-positron-emission tomography/computed tomography findings.

AIM: The aim of this paper is to describe the clinical features of COVID-19-related encephalopathy and their metabolic correlates using brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) imaging. BACKGROUND AND PURPOSE: A variety of neurological manifestations have been reported in association with COVID-19. COVID-19-related encephalopathy has seldom been reported and studied. METHODS: We report four cases of COVID-19-related encephalopathy. The diagnosis was made in patients with confirmed COVID-19 who presented with new-onset cognitive disturbances, central focal neurological signs, or seizures. All patients underwent cognitive screening, brain magnetic resonance imaging (MRI), lumbar puncture, and brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) (FDG-PET/CT). RESULTS: The four patients were aged 60 years or older, and presented with various degrees of cognitive impairment, with predominant frontal lobe impairment. Two patients presented with cerebellar syndrome, one patient had myoclonus, one had psychiatric manifestations, and one had status epilepticus. The delay between first COVID-19 symptoms and onset of neurological symptoms was between 0 and 12 days. None of the patients had MRI features of encephalitis nor significant cerebrospinal fluid (CSF) abnormalities. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. All patients presented with a consistent brain FDG-PET/CT pattern of abnormalities, namely frontal hypometabolism and cerebellar hypermetabolism. All patients improved after immunotherapy. CONCLUSIONS: Despite varied clinical presentations, all patients presented with a consistent FDG-PET pattern, which may reflect an immune mechanism.

Botulinum toxin therapy improves masseter spasticity in Amyotrophic Lateral Sclerosis.

Fifteen ALS patients, with troublesome symptoms linked to masseter spasticity, benefited from BoNT-A injections in each masseter. Based on the medical records of patients, the effect of the first injection was assessed one month later. We retrospectively collected information for 12 patients. Eight of them reported a beneficial effect after the injection for the following symptoms: trismus, tongue, lip and cheek biting, and jaw clonus. Five patients indicated that dental care was easier after injection. Our study showed that injections of BoNT-A unequivocally reduced masseter spasticity in ALS patients who subsequently enjoyed greater comfort in their daily living.

The adolescent and adult form of cobalamin C disease: clinical and molecular spectrum.

BACKGROUND: Cobalamin C disease is the most common inborn error of cobalamin metabolism with an autosomal recessive mode of inheritance and mutations within the MMACHC gene. Clinical features, including systemic, haematological and neurological abnormalities, usually occur in the first year of life. Adolescent and adult onset presentations are rare. METHODS: We report on the clinical, molecular and imaging features in three patients aged 40, 42 and 42 years at the last follow-up. We examine these cases together with eight previously described cases to determine the clinical and molecular features of the disease in adults. RESULTS: Mean age at onset of clinical symptoms was 26 years; clinical features included predominant neurological disturbances and thromboembolic complications. White matter abnormalities on brain MRI were sometimes observed. Most patients (eight of nine patients investigated) were compound heterozygotes for the 271dupA mutation and a missense mutation. Intramuscular or intravenous hydroxycobalamin therapy stopped the progression of the disease and resulted in a better clinical outcome and favourable biological status in 7/9 treated cases, while the two untreated patients died quickly. CONCLUSIONS: As cobalamin C disease and related disorders of homocysteine metabolism are treatable conditions, homocysteinaemia should be included in the investigations of patients with progressive neurological deterioration, unexplained psychiatric disturbances or recurrent thromboembolic events.

[Classical and atypical clinical features in amyotrophic lateral sclerosis]. / Quels sont les signes cliniques, classiques et inhabituels, devant faire évoquer une sclérose latérale amyotrophique?

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving primarily motor neurons in the cerebral cortex, brainstem and spinal cord. In the absence of any biological marker, the diagnosis of ALS is based on clinical analysis, combined with the results of electromyography. Consensus diagnosis criteria (El Escorial criteria) have been developed to define workable and internationally acceptable guidelines for the diagnosis of ALS. A combination of lower and upper motor neuron signs with evidence of spread within a region or to other regions is required. The diagnosis of ALS has been categorized into various levels of certainty depending on the presence of upper motor neuron and lower motor neuron signs together in the same topographical anatomic region (brainstem and cervical, thoracic or lumbosacral spinal cord). Clinical types and patterns of ALS have been defined. The emerging concept of "ALS plus" is characterized by the presence of atypical clinical features, e.g. extrapyramidal signs or dementia, in association with the classical phenotype of ALS. This paper reviews the classical and atypical clinical features of ALS.

[Clinical characteristics of amyotrophic lateral sclerosis subsets]. / Quels sont les critères cliniques de la sclérose latérale amyotrophique en fonction des formes cliniques?

Amyotrophic lateral sclerosis (ALS) is characterized by significant clinical variability. Different subsets are classically individualized: bulbar onset and limb onset ALS, sporadic and familial ALS, ALS-plus syndromes (characterized by the presence of atypical clinical features, e.g. extrapyramidal signs or dementia, in association with the classical phenotype of ALS) and Western Pacific ALS. In addition, ALS-related syndromes include progressive muscular atrophy, primary lateral sclerosis and progressive bulbar palsy. The recognition of ALS subsets and ALS-related syndromes is important in clinical practice since the prognosis may vary depending on the clinical presentation. The prognosis of bulbar-onset ALS is poor compared with the spinal-onset type. Primary lateral sclerosis, defined by pure upper motor neuron findings, has a more benign course than classical ALS. It has also important implications for therapeutic trials to ensure the homogeneity of clinical material since inclusion of atypical forms with different prognoses can skew the outcome analysis. This paper reviews the clinical characteristics of the ALS subsets and ALS-related syndromes.

[Differential diagnosis and atypical subsets of amyotrophic lateral sclerosis]. / Quels sont les diagnostics differentiels et les formes frontières de SLA?

Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of upper and lower motor neurons. In the absence of any validated biological marker, the diagnosis of ALS depends upon recognition of characteristic symptoms and signs together with supportive electrophysiological findings. The diagnosis of ALS is easy to recognize in its fully developed form but during the early stages both false positive and false negative diagnoses are common. In clinical practice, diagnostic difficulties mostly arise with patients who present either with only upper motor neuron, or with only lower motor neuron signs. It may be difficult to distinguish ALS with clinically predominant lower motor neuron involvement from alternative diagnoses including spinal atrophies of adult onset, Kennedy's disease, inclusion body myositis and motor neuropathies with conduction blocks. The diagnosis of ALS related syndromes (progressive muscular atrophy, primary lateral sclerosis and progressive bulbar palsy) requires the elimination of alternate diagnoses. This paper reviews the main characteristics of diseases mimicking ALS and the atypical subsets of ALS.

[Contribution of proton magnetic resonance spectroscopy to the diagnosis of Balo's concentric sclerosis]. / Intérêt de la spectroscopie par résonance magnétique dans la sclérose concentrique de Balo.

INTRODUCTION: Balo's concentric sclerosis is a neuropathological type of multiple sclerosis characterized by alternating rings of spared myelin and demyelination. Diagnosis is based on MRI, but very few data are available concerning the lesion features using serial proton magnetic resonance spectroscopy (1H-MRS). METHODS: We report 1H-MRS initial findings and disease course in one case of Balo's concentric sclerosis. RESULTS: The first 1H-MRS study of 2 concentric ring-enhanced lesions showed a decreased N-acetyl-aspartate (NAA) peak, an increased choline peak, 2 broad lactate peaks and the presence of a lipid peak at 0.9 ppm. Six months later, 1H-MRS showed a decrease of choline peak, whereas the lactate peak had disappeared. The NAA peak was still at a low level. CONCLUSION: These findings are similar to those reported in demyelinating disorders, such as multiple sclerosis. Thus, in Balo's concentric sclerosis, 1H-MRS may provide neurochemical arguments for inflammation and demyelination, and indicate the severity of axonal damage and recovery.

[Physiopathology of ALS: therapeutic approach]. / Physiopathologie de la sclérose latérale amyotrophique: approches thérapeutiques.

The finding in 1993 of a mutation of the copper zinc super oxyde dismutase (SOD1) provides a major breakthrough in the understanding of the etiopathogenic mechanism of amyotrophic lateral sclerosis. Various mechanisms are commonly implied in the motor neurons degeneration. Excitotoxicity and calcium metabolism abnormalities are one of the most frequently confirmed hypotheses. It allowed proposing riluzole which remains the only one drug proved to be active in the disease. The role of growth factors remains controversial and all therapeutic trials performed with these molecules remained negative. Oxidative stress abnormalities are demonstrated by number of studies but their direct therapeutic application remains to be demonstrated. Apoptosis and the role of mitochondria has been definitely confirmed and open a new therapeutic avenue for the next few years.

Reduced capillary perfusion and permeability in human tumour xenografts treated with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR imaging and macromolecular contrast media.

We describe the use of perfusion-permeability magnetic resonance imaging (ppMRI) to study hemodynamic parameters in human prostate tumor xenografts, following treatment with the vascular endothelial growth factor-A (VEGF) receptor tyrosine kinase inhibitor, ZD4190. Using a macromolecular contrast agent (P792), a fast MR imaging protocol and a compartmental data analysis, we were able to demonstrate a significant simultaneous reduction in tumor vascular permeability, tumor vascular volume and tumor blood flow (43%, 30% and 42%, respectively) following ZD4190 treatment (100 mg/kg orally, 24 h and 2 h prior to imaging). This study indicates that MR imaging can be used to measure multiple hemodynamic parameters in tumors, and that tumor vascular permeability, volume and flow, can change in response to acute treatment with a VEGF signaling inhibitor.

[Spinal cord compression secondary to extramedullary hematopoiesis in a patient with thalassemia]. / Compression médullaire par hématopoïèse ectopique chez un patient atteint de bêta-thalassémie.

A 19-year-old man with homozygous beta thalassemia presented with signs of thoracic spinal cord compression secondary to extramedullary hematopoiesis. The patient was treated with hypertransfusion and hydroxyurea. After two months, clinical signs had resolved and magnetic resonance imaging showed significant regression of the extradural mass. Pathophysiology and therapeutic options in this condition are briefly discussed.