A real-world clinical validation for AI-based MRI monitoring in multiple sclerosis.

Modern management of MS targets No Evidence of Disease Activity (NEDA): no clinical relapses, no magnetic resonance imaging (MRI) disease activity and no disability worsening. While MRI is the principal tool available to neurologists for monitoring clinically silent MS disease activity and, where appropriate, escalating treatment, standard radiology reports are qualitative and may be insensitive to the development of new or enlarging lesions. Existing quantitative neuroimaging tools lack adequate clinical validation. In 397 multi-center MRI scan pairs acquired in routine practice, we demonstrate superior case-level sensitivity of a clinically integrated AI-based tool over standard radiology reports (93.3% vs 58.3%), relative to a consensus ground truth, with minimal loss of specificity. We also demonstrate equivalence of the AI-tool with a core clinical trial imaging lab for lesion activity and quantitative brain volumetric measures, including percentage brain volume loss (PBVC), an accepted biomarker of neurodegeneration in MS (mean PBVC -0.32% vs -0.36%, respectively), whereas even severe atrophy (>0.8% loss) was not appreciated in radiology reports. Finally, the AI-tool additionally embeds a clinically meaningful, experiential comparator that returns a relevant MS patient centile for lesion burden, revealing, in our cohort, inconsistencies in qualitative descriptors used in radiology reports. AI-based image quantitation enhances the accuracy of, and value-adds to, qualitative radiology reporting. Scaled deployment of these tools will open a path to precision management for patients with MS.

Presumptive isolated neurosarcoidosis involving eloquent structures: An argument for empirical TNF-α inhibition.

There are clinical and radiological phenotypes characteristic of neurosarcoidosis. Histopathologic confirmation is preferred, however, biopsy is associated with a significant risk of morbidity when only eloquent neural structures are involved and where there is no systemic disease. We present a series of patients with isolated neurosarcoidosis and suggest circumstances where an empirical, closely monitored, trial of tumour-necrosis-factor-alpha inhibitor therapy can improve outcome and diagnostic confidence.

The corpus callosum in the diagnosis of multiple sclerosis and other CNS demyelinating and inflammatory diseases.

Lesions in the corpus callosum (CC) are important radiological clues to the diagnosis of multiple sclerosis (MS), but may also occur in other neuroinflammatory and non-neuroinflammatory conditions. In this article, we discuss the radiological features of lesions within the CC in MS and other central nervous system inflammatory and acquired demyelinating diseases. An understanding of the appearance and location of lesions in the CC is important not only for accurate diagnosis and treatment of these various conditions, but as it also provides insights into pathogenesis.

Decoding diffusivity in multiple sclerosis: analysis of optic radiation lesional and non-lesional white matter.

OBJECTIVES: Diffusion tensor imaging (DTI) has been suggested as a new promising tool in MS that may provide greater pathological specificity than conventional MRI, helping, therefore, to elucidate disease pathogenesis and monitor therapeutic efficacy. However, the pathological substrates that underpin alterations in brain tissue diffusivity are not yet fully delineated. Tract-specific DTI analysis has previously been proposed in an attempt to alleviate this problem. Here, we extended this approach by segmenting a single tract into areas bound by seemingly similar pathological processes, which may better delineate the potential association between DTI metrics and underlying tissue damage. METHOD: Several compartments were segmented in optic radiation (OR) of 50 relapsing-remitting MS patients including T2 lesions, proximal and distal parts of fibers transected by lesion and fibers with no discernable pathology throughout the entire length of the OR. RESULTS: Asymmetry analysis between lesional and non-lesional fibers demonstrated a marked increase in Radial Diffusivity (RD), which was topographically limited to focal T2 lesions and potentially relates to the lesional myelin loss. A relative elevation of Axial Diffusivity (AD) in the distal part of the lesional fibers was observed in a distribution consistent with Wallerian degeneration, while diffusivity in the proximal portion of transected axons remained normal. A moderate, but significant elevation of RD in OR non-lesional fibers was strongly associated with the global (but not local) T2 lesion burden and is probably related to microscopic demyelination undetected by conventional MRI. CONCLUSION: This study highlights the utility of the compartmentalization approach in elucidating the pathological substrates of diffusivity and demonstrates the presence of tissue-specific patterns of altered diffusivity in MS, providing further evidence that DTI is a sensitive marker of tissue damage in both lesions and NAWM. Our results suggest that, at least within the OR, parallel and perpendicular diffusivities are affected by tissue restructuring related to distinct pathological processes.

Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions.

OBJECTIVE: To investigate the potential links between thinning of retinal ganglion cell axons in eyes of patients with multiple sclerosis (MS) without past optic neuritis (ON) and MS-related inflammatory damage of the posterior visual pathway. METHODS: Temporal retinal nerve fiber layer (tRNFL) thickness was analyzed in eyes with no history of ON (NON) from 53 patients with relapsing-remitting MS. Fifty normal age- and sex-matched controls were examined with optical coherence tomography. Low-contrast visual acuity charts were used for functional assessment of vision. The optic tract (OT) and optic radiation (OR) were identified using probabilistic tractography, and volume of T2 fluid-attenuated inversion recovery lesions and diffusion tensor imaging (DTI) indices were measured within both structures. Cross-sectional diameter of the OT was also calculated. RESULTS: tRNFL thickness was significantly reduced in NON eyes and was associated with reduced low-contrast visual acuity. Lesions within the OR were detected in the majority of patients. There was a significant correlation between thinning of the tRNFL and OR lesion volume (adjusted for non-OR lesion volume, age, sex, and disease duration). tRNFL thickness also correlated with OR DTI indices. No OT lesions were identified in any of the patients and no relationship between retinal nerve fiber layer loss and potential markers of OT lesions was found. CONCLUSION: The results demonstrate a strong tract-specific association between loss of tRNFL fibers and MS-related inflammation within OR.

Lhermitte-Duclos disease presenting with atypical positional nystagmus.

We describe a patient with dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease) who presented with an acute onset of positional disequilibrium. Video-oculography in the right Hallpike position revealed rightward torsional down-beat nystagmus, initially thought to be right anterior canal benign positional vertigo. However, the presence of spontaneous nystagmus, the persistent character of the positional nystagmus and the absence of fatigability indicated central positional nystagmus, attributable to his right-sided Lhermitte-Duclos disease. These findings emphasise the need for clinicians to reconsider a central cause before diagnosing the rare anterior canal benign positioning vertigo variant.

An unusual case of a pituitary fossa aspergilloma in an immunocompetent patient mimicking infiltrative tumour.

Sellar aspergillosis is a rare infection commonly mistaken for a pituitary tumour. We present a rare case of pituitary fossa Aspergillus fumigatus mycetoma in an immunocompetent 90-year-old female, who presented with headaches. Magnetic resonance imaging scans demonstrated an enhancing pituitary fossa mass that appeared to infiltrate the sphenoid sinus, suggestive of an invasive tumour. Stereotactic trans-sphenoidal resection confirmed localized A. fumigatus infection. The abscess was debrided and the dura was left intact. Her headaches resolved post-operatively and she was treated with voriconazole. This indicates that aspergilloma should be considered as a differential for an unexplained pituitary lesion even in elderly immunocompetent patients.

Spontaneous low pressure headache - a review and illustrative patient.

Low pressure headache typically occurs as a complication of dural puncture. "Spontaneous" low pressure headache is a relatively rare but under-recognised cause of intractable headache. Clinical suspicion of this condition warrants imaging of the brain to confirm the diagnosis; spinal imaging may be needed to identify the site of the leak. Epidural blood patching may be necessary to seal the leak - CT fluoroscopy may be helpful in delivering the patch directly to the site of the leak. Surgical intervention may be required in intractable cases. We describe a patient with spontaneous intracranial hypotension and review the clinical and radiological features of this syndrome.

Expanding the clinical, radiological and neuropathological phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of the CNS with a predilection for the hindbrain and responsive to immunotherapy. Five further cases are described with detailed pathology and long term evaluation. CLIPPERS does not represent a benign condition, and without chronic immunosuppression the disease may relapse. The radiological distribution is focused not only in the pons but also in the brachium ponti and cerebellum. Pontocerebellar atrophy occurred early, even in cases treated promptly. Significant cognitive impairment was seen in some cases and was associated with additional cerebral atrophy. The pathology included distinctive histiocytic as well as lymphocytic components and evidence of neuro-axonal injury. Additional subclinical systemic findings on investigation were identified. Relapse was associated with withdrawal of corticosteroids, and disability was least marked in cases where both the presentation and relapses were treated promptly. We propose that the title of the syndrome be amended to chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids to more accurately reflect the distribution of the radiological findings.

What lies beneath the tent? JC-virus cerebellar granule cell neuronopathy complicating sarcoidosis.

A 49-year-old, HIV-negative woman with sarcoidosis presented with a subacute unilateral cerebellar syndrome. A brain MRI revealed a hyperintense lesion without mass effect in the left cerebellar hemisphere, but no pathology above the tentorium. Steroid therapy for presumed neurosarcoidosis was ineffective and the patient deteriorated progressively. Cerebellar biopsy showed abnormal granule cells and demyelination. Immunocytochemistry confirmed the diagnosis of progressive multifocal leucoencephalopathy (PML) with JC (John Cunningham) virus granule cell neuronopathy. The patient succumbed to progressive brainstem dysfunction despite treatment with cidofovir. Although rare, PML should be considered in all patients with impaired cell-mediated immunity and unexplained neurological dysfunction, even in the absence of HIV infection.

Post-vaccination encephalomyelitis: literature review and illustrative case.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that is usually considered a monophasic disease. ADEM forms one of several categories of primary inflammatory demyelinating disorders of the central nervous system including multiple sclerosis, optic neuropathy, acute transverse myelitis, and neuromyelitis optica (Devic's disease). Post-infectious and post-immunisation encephalomyelitis make up about three-quarters of cases, where the timing of a febrile event is associated with the onset of neurological disease. Post-vaccination ADEM has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, hepatitis B, and the Hog vaccine. We review ADEM with particular emphasis on vaccination as the precipitating factor. We performed a literature search using Medline (1976-2007) with search terms including "ADEM", "acute disseminated encephalomyelitis", "encephalomyelitis", "vaccination", and "immunisation". A patient presenting with bilateral optic neuropathies within 3 weeks of "inactivated" influenza vaccination followed by delayed onset of ADEM 3 months post-vaccination is described.

Post-cranial irradiation syndrome with migraine-like headaches, prolonged and reversible neurological deficits and seizures.

Two adult patients with a background history of astrocytomas treated with resection and cranial irradiation, 18 and 16 years previously, presented with acute onset of headache associated with prolonged neurological deficits, including dysphasia and right hemiparesis. The first patient also developed seizures while in hospital. In both patients, magnetic resonance imaging brain scans failed to show evidence of acute ischaemia or tumour recurrence and symptoms reversed completely after 1 month and 7 days, respectively. A single photon emission computed tomography scan, performed on the first patient at day 8 post-admission, showed hyperperfusion in the left parieto-occipital region (in the same region as his previous tumour). The clinical histories and outcomes are consistent with the diagnosis of post-cranial irradiation syndrome with migraine-like headaches and prolonged and reversible neurological deficits. Recognition of this disorder is useful in providing reassurance of a favourable prognosis and may also help avoid invasive investigations.

Positional vomiting due to a thoracic spinal dural arteriovenous fistula. Case report.

The authors report the unique case of a patient with a thoracic spinal dural arteriovenous fistula (DAVF) causing remote brainstem symptoms of positional vomiting and minimal vertigo. Magnetic resonance (MR) imaging of the brain demonstrated high signal abnormality in the medulla, presumably related to venous hypertension, and spinal MR imaging revealed markedly dilated veins along the dorsal aspect of the cord. Spinal angiography confirmed the presence of a thoracic spinal DAVF. Disconnection of the DAVF from the spine resulted in a marked improvement in symptoms and resolution of the preoperative MR imaging-documented abnormalities. The authors highlight the rare syndrome of positional vomiting as a brainstem symptom and conclude that spinal DAVFs should be considered in the differential diagnosis of high signal MR imaging abnormalities localized to the brainstem.