Signs Of Leukoencephalopathy Research Articles

LINC-11. Intrathecal methotrexate in a young child with medulloblastoma with extensive nodularity. An alternative to intra-ventricular route in Low and Middle Income Countries?

BACKGROUND: In places where determination of molecular subgrouping of Medulloblastoma is not available, histology remains standard for risk stratification and treatment. Young children with medulloblastoma treated with craniospinal irradiation show a negative impact in neurocognitive functions, thus avoiding radiation in this specific population is encouraged. High dose chemotherapy and stem cell rescue have been internationally used as a strategy to spare radiation in infants and young children with Medulloblastoma. German HIT protocol (SKK) reported a PFS 85±8 % and good cognitive outcome in patients with Desmoplastic Medulloblastoma treated with intra-ventricular (i.vtr.) methotrexate (MTX). SKK protocol includes 36 i.vtr. administrations of MTX through a subcutaneous reservoir. Complications related to the use of this kind of reservoir could be due to the lack of experienced staff. METHODS: We report a patient with localized Medulloblastoma with extensive nodullarity (MBEN) treated as per SKK using intrathecal route instead of i.vtr MTX. A 2.5 year old boy was diagnosed with MBEN, surgery was complete and no shunt was required. Spinal MRI and CSF cytology were negative. Patient received 3 cycles of SKK protocol and 2 cycles of modified SKK. During the first 3 cycles he received one dose of intrathecal MTX 8mg on weeks 1, 3, 5 and 7 (12 doses in all). Patient remains free of disease 2 years after chemotherapy completion and without signs of leukoencephalopathy on T2 weighted cranial MRI. DISCUSSION: Intrathecal administration of MTX is commonly used for the treatment of Acute Lymphoblastic Leukemia, the most common childhood cancer. Staff in Low and Middle Income Countries (LMIC) may be better trained for such procedure than using a ventricular access device. This strategy could be considered when using SKK protocol in selected young children with Demoplastic Medulloblastoma and MBEN in LMIC where centers with enough experience with ventricular access device placement and handling are scarce.

Cognitive and Emotional Disorders in Patients with Migraine and Signs of Leukoencephalopathy

Cognitive and Emotional Disorders in Patients with Migraine and Signs of Leukoencephalopathy

Cognitive and emotional disorders in patients with migraine and signs of leukoencephalopathy

To identify cognitive and emotional disorders and their correlation with neuroimaging parameters in patients with chronic migraine. We examined 50 patients (8 men and 42 women, mean age 41.9±11.9 years) with migraine, including 31 with chronic migraine, and signs of leukoencephalopathy according to magnetic resonance imaging (MRI). A control group comprised 40 healthy individuals (13 men and 27 women) aged 20 to 64 years (mean 42.6±12.0 years). A number of tests for neuropsychological examination and assessment of the emotional state, including a 12-word test, literal and categorical associations, Benton Test, the Montreal cognitive scale (MOCA), the Hospital Depression Scale, the Beck Depression Scale, the Center for Epidemiological Research scale, the Hospital Anxiety Scale and the Spielberger-Khanin scale, were administered at baseline and after 3 and 6 month of preventive therapy. Patients with migraine had lower scores (p=0.004) on MOCA, memorization of 12 words (p=0.0003), test for literal (p=0.001) and categorical associations (p=0.0002) compared with the control group. No significant correlations were found between the volume of white matter lesions according to MRI and the severity of cognitive impairment. An inverse correlation of average strength was noted (correlation coefficient R=-0.41) between the number of days with headache per month and the MOCA score (p<0.05). In patients with migraine, signs of depression were found on the Hospital Depression Scale (p=0.04), Beck Depression Scale (p=0.003), the Center for Epidemiological Research scale (p=0.0001), and increased anxiety on the Hospital Anxiety Scale (p=0.0001) and the Spielberger-Khanin scale (p=0.0001). A significant relationship was found between the degree of depression and the MOCA score (p=0.007). The frequency of headaches decreased from 19.4±2.9 to 12.6±4.4 days per month (p<0.05). There were a significant decrease of emotional disorders and improvement of cognitive functions compared with baseline scores during the 6 month therapy. Preventive treatment of migraine and concomitant emotional disorders seems to be the most effective way to improve cognitive functions.

Cognitive and emotional impairment in patients with migraine and signs of leukoencephalopathy during preventive therapy

Patients with migraine and signs of leukoencephalopathy are frequently found to have cognitive impairment (CI), the pathogenesis of which is not entirely clear. The dynamics of CI in these patients during preventive therapy has been little studied.Patients and methods. A six-month follow-up study was conducted in 50 patients (8 men and 42 women; mean age, 41.9±11.9 years) with migraine (mainly chronic one) and signs of cerebral leukoencephalopathy according to magnetic resonance imaging (MRI). A control group consisted of 40 healthy individuals (13 males and 27 females) aged 20 to 64 years (mean age, 42.6±12.0 years). Neuropsychological examinations (the 12-word recall test; the test of literal and categorical associations; the Benton visual retention test, the Munsterberg test; the Montreal Cognitive Assessment (MoCA), the trail making test; the forward and backward digit recall test; the digit-symbol coding test; and the Stroop color test) and studies of emotional disorders (the Beck Depression Inventory (BDI), the Center for Epidemiological Studies Depression Scale (CES-D); the Hospital Anxiety and Depression Scale (HADS), and the Spielberger-Khanin Scale) were performed at baseline, and at 3 and 6 months of preventive therapy for migraine.Results and discussion. The patients with migraine versus the control group were observed to have lower scores of the MoCA (p=0.004), the 12- word recall test (p=0.0003), and the tests of literal (p=0.001) and categorical (p=0.0002) associations. No significant relationship was found between the volume of MRI cerebral white matter lesions and the severity of CI. There was a moderate inverse correlation (correlation coefficient R=-0.41) between the number of headache (HA) days per month and the MoCA score (p&lt;0.05). The patients with migraine were found to have the signs of depression on the Hospital Depression Scale (p=0.04), the BDI (p=0.003), and the CES-D Scale (p=0.0001) and increased anxiety on the HADS (p=0. 0001) and the Spielberger–Khanin Scale (p=0.0001). There was a significant association between the degree of depression and the MoCA score (p=0.007). During 6-month preventive therapy, there was a decline in the incidence of HA from 19.4±2.9 to 12.6±4.4 days per month (p&lt;0.05), a significant reduction in the severity of emotional disorders, and an improvement in cognitive functions by most neuropsychological tests (the MoCA, the 12-word recall test, the Munsterberg test, and the trail making test Part B) compared to the baseline data.Conclusion. During preventive treatment for migraine, there was a reduction in the frequency of HA attacks and in the severity of emotional and cognitive impairment. The preventive treatment of migraine and related emotional disorders seems to be the most effective way to improve cognitive functions.

Tumefactive demyelination, an uncommon form of tacrolimus neurotoxicity

The immunosuppressant tacrolimus (FK 506) is widely used in transplantation medicine, although it has neurotoxic side effects. The neurotoxicity of tacrolimus to the CNS consists mainly of leukoencephalopathy with clinical and radiologic features similar to posterior reversible encephalopathy syndrome (PRES).1 The neurologic symptoms and signs of leukoencephalopathy usually develop within 3 months of commencing treatment with tacrolimus.1 We describe a patient who developed tumefactive inflammatory demyelinating lesions as an atypical manifestation of tacrolimus neurotoxicity. ### Case report. A 54-year-old woman with hepatocellular carcinoma underwent cadaver liver transplantation in May 2009. After transplantation, she was treated with tacrolimus 0.075 mg/kg and mycophenolate mofetil 250 mg BID. In September 2009, she developed slurred speech and right-side weakness 2 days before admission. Brain MRI scanned 2 days after symptoms onset showed 2 large mass-like lesions in the left corona radiata and frontal lobe. The lesions were hyperintense on T2-weighted images with an open ring pattern on gadolinium enhancement (figure,A). The serum tacrolimus level was 8.5 ng/mL (therapeutic range 5.0–15.0 ng/mL). The CSF analysis showed normal cell count, but elevated total protein level (103 mg/dL). Oligoclonal bands were absent and …

High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study

BackgroundTo improve survival of elderly patients with primary central nervous system lymphoma (PCNSL), we conducted a phase II study with high-dose methotrexate (MTX) combined with procarbazine and CCNU. To reduce neurotoxicity, whole-brain irradiation was reserved for patients not responding to chemotherapy. Patients and methodsHigh-dose MTX was applied on days 1, 15, and 30, procarbazine on days 1–10, and CCNU on day 1. Study treatment comprised up to three 45-day cycles. There was no lower limit of Karnofsky performance status (KPS). ResultsThirty patients with PCNSL (n = 29) or primary ocular lymphoma (n = 1) were included (median age 70 years, range 57–79 years). The median initial KPS was 60% (range 30%–90%). Best documented response in 27 assessable patients were 12 of 27 (44.4%) complete remissions, 7 of 27 (25.9%) partial remissions, and 8 of 27 (29.6%) disease progressions. Two patients died of probable treatment-related causes. With a median follow-up of 78 months (range 34–105), the 5-year overall survival is 33%. Eight of 30 patients (26.7%) are currently alive and well, six without signs of leukoencephalopathy. ConclusionThe combination of high-dose MTX with procarbazine and CCNU is feasible and effective and results in a low rate of leukoencephalopathy. Comorbidity and toxicity remain of concern when treating PCNSL in elderly patients.

A familial disorder with subcortical ischemic strokes, dementia, and leukoencephalopathy

A family had a disorder characterized by (1) a pattern suggestive of autosomal dominant inheritance, (2) recurrent attacks of focal brain deficits starting in mid adulthood and often leading to severe motor disability with pseudobulbar palsy and dementia of the subcortical type, and (3) neuroimaging evidence of leukoencephalopathy and well-circumscribed lesions consistent with small deep infarcts. Some affected members were clinically asymptomatic but had MRI signs of leukoencephalopathy. Extensive investigations failed to uncover a previously described recognizable genetic disorder.

Progression of methotrexate-induced leukoencephalopathy in children with leukemia.

From 1972-1974, 228 children began treatment for acute lymphocytic leukemia and were prospectively assessed for neurologic complications. After CNS irradiation (2,400 rad) and intrathecal methotrexate (MTX), they received weekly intravenous maintenance therapy with MTX alone (40-60 mg/m2; 20 patients) or MTX (10-30 mg/m2) with other drugs (208 patients). Signs of leukoencephalopathy appeared in 11 children (nine without CNS leukemia) after 4-15 months of IV MTX alone, and included lethargy, seizures, spasticity, paresis, drooling, and dementia. Before or during the clinical onset, EEG frequencies slowed (all ten patients tested). Radionuclide scans showed periventricular accumulation of 99mTc (9/11 patients) and remained abnormal for greater than or equal to six months in eight patients. Cranial computed tomograms or neuropathology findings (five patients each) demonstrated leukoencephalopathy (nine patients) and radiation-related microangiopathy (ten patients). Severe neurologic and neuropsychologic dysfunctions were present in four long-term survivors.