Non-enhancing White Matter Lesions Research Articles

Progressive Multifocal Leukoencephalopathy in a Patient With Cirrhosis and Hepatocellular Carcinoma

The following case describes a constellation of progressive cognitive and motor deficits in a 73-year-old man with cirrhosis and history of early-stage hepatocellular carcinoma confined to his liver. He had deficits in calculation, language, and writing, as well as subtle right-sided weakness. Magnetic resonance imaging (MRI) of the brain demonstrated non-enhancing white matter lesions without mass effect in the bilateral parietal and left occipitotemporal regions, correlating with neurologic exam findings. The patient’s basic blood and cerebrospinal fluid (CSF) studies were within normal limits. Our differential included inflammatory and demyelinating conditions, hepatic encephalopathy, posterior reversible encephalopathy syndrome, progressive multifocal leukoencephalopathy (PML), and central nervous system (CNS) tumors. He did not improve with an empiric course of high-dose steroids or adequate hepatic encephalopathy treatment. A repeat lumbar puncture sent for additional CSF studies revealed a positive John Cunningham (JC) virus PCR test, confirming diagnosis of PML. Although the patient did not have any known overt immunosuppressive condition or treatment, the patient’s cirrhosis and age placed him at higher risk for developing JC virus CNS reactivation. In a published case series of patients with PML and no classic immunosuppressive condition that includes several patients with concomitant cirrhosis, prognosis is much worse compared to those with known, reversible causes of immunosuppression.

Blood-brain barrier breakdown in non-enhancing multiple sclerosis lesions detected by 7-Tesla MP2RAGE ΔT1 mapping.

Although the blood-brain barrier (BBB) is altered in most multiple sclerosis (MS) lesions, gadolinium enhancement is seen only in acute lesions. In this study, we aimed to investigate gadolinium-induced changes in T1 relaxation time in MS lesions on 7-tesla (7T) MRI as a means to quantify BBB breakdown in non-enhancing MS lesions. Forty-seven participants with MS underwent 7T MRI of the brain with a magnitude-prepared rapid acquisition of 2 gradient echoes (MP2RAGE) sequence before and after contrast. Subtraction of pre- and post-contrast T1 maps was used to measure T1 relaxation time change (ΔT1) from gadolinium. ΔT1 values were interrogated in enhancing white matter lesions (ELs), non-enhancing white matter lesions (NELs), and normal appearing white matter (NAWM) and metrics were compared to clinical data. ΔT1 was measurable in NELs (median: -0.139 (-0.304, 0.174) seconds; p < 0.001) and was negligible in NAWM (median: -0.001 (-0.036, 0.155) seconds; p = 0.516). Median ΔT1 in NELs correlated with disability as measured by Expanded Disability Status Scale (EDSS) (rho = -0.331, p = 0.026). Multiple measures of NEL ΔT1 variability also correlated with EDSS. NEL ΔT1 values were greater and more variable in patients with progressive forms of MS and greater in those not on MS treatment. Measurement of the changes in T1 relaxation time caused by contrast on 7T MP2RAGE reveals clinically relevant evidence of BBB breakdown in NELs in MS. This data suggests that NEL ΔT1 should be evaluated further as a biomarker for disease severity and treatment effect in MS.

Retrospective, dual-centre review of imaging findings in neurosarcoidosis at presentation: prevalence and imaging sub-types

To assess the prevalence of various imaging manifestations in neurosarcoidosis (NS) patients at presentation and to explore if specific imaging findings may cluster in different sub-groups. A retrospective, dual-institution, systematic imaging review was undertaken of the magnetic resonance imaging (MRI) findings in 100 consecutive NS patients who presented over a 15-year period. Clustering analysis (k-mode) was performed to evaluate co-occurrence of imaging findings. Non-enhancing white matter (NEWM) lesions were the most common imaging abnormality (56%), followed by leptomeningeal (47%) and pachymeningeal (32%) involvement. Other common manifestations included cranial nerve involvement (30%), parenchymal granulomas (27%), hypothalamic-pituitary-adrenal axis involvement (26%), and hydrocephalus (14%). Additionally, a higher prevalence of perivascular enhancement (23%), cerebrovascular events (including ischaemic and haemorrhagic events; 17%), and ependymal involvement (20%) were noted than recognised previously. Additional k-mode analysis was performed to explore underlying disease sub-clusters. This was evaluated for clusters varying between two though five (k=2-5). For k=4, the analysis revealed that the imaging findings may possibly be divided into disease sub-sets of four groups, each with varying distribution of imaging manifestations and clinical manifestations. Overall, NEWM lesions and meningeal involvement are the most common imaging manifestations of NS. The prevalence of perivascular enhancement, cerebrovascular events, and ependymal involvement is likely higher than reported previously. Additionally, different imaging findings in NS may cluster together and imaging subtypes in NS possibly exist.

Neurological deficit following stereotactic radiosurgery for trigeminal neuralgia

We report a unique case of neurological deficit from late onset multiple sclerosis (MS), in a 65-year-old woman, after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). At 3.5months post-SRS for TN, the patient developed ataxia and left leg paraesthesiae and brain MRI showed altered signal and enhancement in the vicinity of the right trigeminal root entry zone (REZ). The symptoms remitted following treatment with intravenous methylprednisolone, however, 10months post-SRS, the patient developed gait ataxia and left lower limb weakness. MRI showed persistent T2 changes at the REZ and multiple new non-enhancing white matter lesions in the cerebrum and spinal cord; and oligoclonal bands were present in the cerebrospinal fluid but not serum. A diagnosis of multiple sclerosis (MS) was made. This report raises the issue of whether the risk of radiation-induced toxicity is increased in patients with MS treated with SRS. We hypothesise that breakdown in the blood brain barrier secondary to the radiosurgery may have triggered a vigorous local inflammatory response.

Two cases of multinodular and vacuolating neuronal tumour

An unusual multinodular and vacuolating neuronal tumour (MVNT) has been described in the cerebral hemispheres of ten patients with adult-onset seizures. We report the findings in two cases with similar features, a surgical resection and the other an autopsy specimen.Case 1, a 34-year-old female, underwent surgical resection for a multinodular non-enhancing frontal white matter lesion causing intractable epilepsy. Case 2, presented with motor neurone disease (MND) at the age of 71 and MRI scanning revealed extensive multinodular non-enhancing white matter lesions in the temporal lobe. There was no history of epilepsy and post mortem histology confirmed MND.Macroscopically multiple small grey well-formed, discrete and coalescent nodules were seen in the deep cortex and subcortical white matter. On histology, mature-looking neurons with large cytoplasmic vacuoles were distributed in a fibrillary background, where vacuoles were also noted. In the resected tumour scattered oligodendroglia-like cells were present. No ganglion cells were seen. The vacuolated cells exhibited immunopositivity for synaptophysin, HuC/HuD and p62 but were negative for NeuN, neurofilament, GFAP, IDH1, nestin and CD34. Electron microscopy showed non-membrane bound cytoplasmic vacuoles in the neurons and in some neuronal processes. The seizures recurred in Case 1.Some clinicopathological features of this lesion suggest a possible relationship with dysembryoplastic neuroepithelial tumour (DNT) although the morphological features are not typical of DNT. Case 2 demonstrates that MVNT may remain asymptomatic.

The Central Nervous System Phenotype of X-Linked Charcot-Marie-Tooth Disease

We describe 2 patients with X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) disease and central nervous system manifestations and review 19 cases from the literature. Our first case had not been previously diagnosed with Charcot-Marie-Tooth disease, and the second case, although known to have Charcot-Marie-Tooth disease, was suspected of having CMTX1 after presentation with central nervous system manifestations. The most common central nervous system manifestations were transient and included dysarthria, ataxia, hemiparesis, and tetraparesis resembling periodic paralysis. Of the 21 patients, 19 presented at 21 years of age or younger, implicating CMTX1 with transient central nervous system manifestations as a disorder that predominantly affects children and adolescents. CMTX1 should be included in the differential diagnosis of patients who present with transient central nervous system phenomena, including stroke-like episodes, tetraparesis suggestive of periodic paralysis, dysarthria, ataxia, or combinations of these deficits. Reversible, bilateral, nonenhancing white matter lesions and restricted diffusion on magnetic resonance imaging are characteristic features of the central nervous system phenotype of CMTX1.

Mimicry between mitochondrial disorder and multiple sclerosis

Under certain conditions or at certain stages of the disease course, multiple sclerosis (MS) and mitochondrial disorder (MID) may be differential diagnoses and thus may be confused with each other. In a 30 years old female MS was diagnosed at age 16 year upon recurrent sensory disturbances of the right lower leg, an "inflammatory" cerebrospinal fluid, and a cerebral MRI with multiple non-enhancing white matter lesions. Steroids were repeatedly given but because of rapid deterioration treatment was switched to interferon and mitoxantrone, without improvement. Fourteen years after onset the patient additionally presented with a history of rhabdomyolysis, hypothyroidism, ophthalmoparesis, anarthria, tetraspasticity, tetraparesis, and joint contractures. After MID had been diagnosed in her mother she was re-evaluated and elevated resting lactate, axonal polyneuropathy, and empty sella were additionally found. Muscle biopsy revealed myophagy, fat deposition, and type-II predominance, and biochemical investigations showed a deficiency of complex I and IV of the respiratory chain. MID was diagnosed also in the index patient. It is concluded that even if CSF investigations or imaging studies suggest MS, differentials such as MIDs need to be excluded before prescribing medication possibly toxic to a MID. An "inflammatory CSF" may also occur in MIDs.

Correlation of MR Imaging Findings and Clinical Manifestations in Neurosarcoidosis

MR imaging is widely used for the diagnosis and follow-up of neurosarcoidosis lesions. However, the temporal evolution of imaging abnormalities and the prognostic significance of imaging features is not well understood. We undertook a retrospective study of patients with biopsy-proved or clinically diagnosed neurosarcoidosis for the following reasons: 1) to assess concordance between abnormalities noted on MR imaging with neurologic symptoms at presentation; 2) to correlate changes in imaging findings during follow-up with clinical improvement or worsening; and 3) to identify imaging features that may have prognostic significance. We reviewed radiologic records from 1999 to 2008 of patients with biopsy-proved or clinically diagnosed neurosarcoidosis and correlated MR imaging findings in these patients with their demographic characteristics, clinical features, and symptomatic responses during follow-up. Thirty-two patients were included in the study. Cranial nerve lesions and leptomeningeal disease identified on MR imaging were symptomatic in 64% patients, dural lesions were associated with symptoms in 28% patients, but nonenhancing white matter lesions did not have correlating symptoms. During follow-up, MR imaging findings generally changed in concordance with the change in clinical symptoms (80% patients). Cranial nerve enhancement (9/11) and spinal lesions (5/8) were most likely to resolve with clinical improvement, whereas dural lesions (6/11), enhancing parenchymal lesions (3/7), and non-enhancing parenchymal lesions (0/4) were less likely to change during therapy. Patients with > or =1 enhancing T2-hypointense lesion (4/7, 57%) were less likely to show clinical improvement than those without such lesions (12/13, 92%). Although many sarcoid-related MR imaging abnormalities were not associated with correlating symptoms at presentation, there was a high degree of concordance between changes in clinical symptoms and MR imaging abnormalities during follow-up. Enhancing T2-hypointense dural and parenchymal lesions were associated with suboptimal imaging and clinical response to immunosuppressive therapy.

Infratentorial progressive multifocal leucoencephalopathy (PML) in a patient with SLE (2008: 4b)

Progressive multifocal leucoencephalopathy (PML) is a viral infection occurring in immunocompromised patients. The typical magnetic resonance imaging (MRI) findings include supratentorial asymmetric nonenhancing white matter lesions without mass effect. We present a patient with progressive cerebellar and brain stem lesions, emphasizing the fact that the diagnosis of PML should be considered also in cases with selective infratentorial involvement.

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY AFTER RITUXIMAB IN A CASE OF NON-HODGKIN LYMPHOMA

Progressive multifocal leukoencephalopathy (PML) is a rare and usually fatal demyelinating disorder caused by the reactivation of a latent JC virus infection. In non-HIV patients, PML usually occurs as a late consequence of hematologic malignancies or immunodeficiency or after severe and prolonged immunosuppression for transplantation or systemic disease. We report a patient who developed PML shortly after diagnosis of non-Hodgkin lymphoma, with a short course of modest immunosuppression including treatment with rituximab. ### Case report. A 63-year-old woman was diagnosed with low-grade non-Hodgkin lymphoma and began chemotherapy 2 weeks later with rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone (R-CHOP). During the third cycle, approximately 7 weeks after beginning treatment, she developed change in mental status with persistent headaches. A brain MRI showed an enhancing white matter abnormality in the right temporal lobe and nonenhancing white matter lesions in the left temporal lobe, right cerebellum, left midbrain, and right pons. Serum chemistries and metabolic studies were …

MRI in detection of brain metastases at initial staging of small-cell lung cancer.

We prospectively investigated 40 patients with small-cell carcinoma of the lung (SCLC) for signs of brain metastasis by neurological examination and MRI of the brain, to determine the significance of MRI for staging. MRI could not be completed in one patient, who was excluded from the study. The MRI studies of the remaining patients showed no abnormalities in 12, cerebral infarcts in 2 and brain metastases in 11 patients, of whom 3 no relevant symptoms. Nonenhancing white matter lesions were found in 14 patients. In 3 of the 4 patients with an abnormal neurological examination at diagnosis, nonenhancing white matter lesions later developed into contrast enhancing lesions compatible with brain metastases; in 2, this occurred during the course of the chemotherapy. MRI did not change the clinical staging in patients with asymptomatic brain metastases.

Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. A review of the literature with a report of sixteen cases.

Progressive multifocal leukoencephalopathy, a common complication of infections with human immunodeficiency virus (HIV), occurs in as many as 3.8% of patients with the acquired immunodeficiency syndrome (AIDS). We report 16 cases and review 12 previously reported cases of progressive multifocal leukoencephalopathy associated with HIV infection. This illness was the presenting manifestation of HIV infection in 8 cases. Limb weakness, gait abnormalities, visual loss, aand altered mental status were the commonest initial complaints. Computed tomography of the brain frequently showed hypodense, nonenhancing white matter lesions. Magnetic resonance imaging was more sensitive than computed tomography in detecting lesions. Cerebrospinal fluid analysis and electroencephalography were nondiagnostic. Impaired cell-mediated immunity was typically noted, even in the absence of other immunodeficiency-associated illnesses. Death occurred within 10 days to 18 months of the onset of symptoms in 22 patients. However, 4 patients remain alive at 3 to 23 months; of these 4, 2 have had significant improvement without treatment. Various therapies were unsuccessful.