Cognitive Dysfunction in Multiple Sclerosis

Cognitive Dysfunction in Multiple Sclerosis Stavra Romas, MD Neurologist, Cognitive Division IMSMP Cognitive Symptoms in MS • What is the person experiencing? • What is causing the complaints? • What can we do about it in terms of medical management? Overview of Cognitive Symptoms • 40-50% have cognitive symptoms • 10% meet criteria for dementia • Cognitive symptoms can occur early • Information doesn’t increase fears (Segal et al., 2006) • Screening is important Assessment of Cognitive Symptoms • • • • • • Medical History and Medication Educational and Employment history Psychosocial history Family history MRI Brief Neuropsychological screen (Rao et al., 1990) • Neuropsychological Battery Factors Causing Cognitive Symptoms MS lesions Mood/Affect Sleep/Fatigue Medication Attention Deficits How MS lesions Affect Cognition • • • • Lesion load Atrophy Normal appearing white matter Other factors? Lesion load • Cognitive Impairment in Multiple Sclerosis (MS) patients is related with the lesion burden. • Frontal Lobe Cognitive decline is related with the corresponding regional lesion load. • Both lesion load and lesion location can be important (Fillipi, 2000) Lesion Load Three factors play a role in the Pathogenesis of cognitive dysfunction: 1) Lesion load 2) The severity of the damage within individual lesions 3) Normal appearing white matter (Filippi, 2000) Brain Atrophy • Multiple studies with variable results • Methods of estimating brain atrophy vary considerably • (Hildebrandt, Multiple Sclerosis, 2006) correlation between memory performance and relative ventricular width. MRI Findings Never Explain the Whole Picture • NAWM? • Temporal course or age at onset? • Other factors? Factors Causing Cognitive Symptoms MS lesions Mood/Affect Sleep/Fatigue Medication Attention Deficits Disorders of Mood and Affect • • • • Depression • Euphoria/lability Anxiety • Pseudobulbar Bipolar Symptoms symptoms Psychotic Symptoms Neuropsychiatric MS • Multiple case reports of pure neuropsychiatric presentation of MS • Lyoo at al,1996 performed brain MRI on 2,783 inpatients referred as part of psychiatric evaluation • 53 patients (1.9%) had WM pattern consistent with MS Neuropsychiatric MS Suspect MS: • Lack of previous psychiatric history • Late-onset or atypical features • Lack of response to standard treatments • Cognitive changes • Neurological findings • MRI findings, particularly atrophy or lesions in WM of the cerebral hemispheres (Asghar-Ali, 2004) Factors Causing Cognitive Symptoms MS lesions Mood/Affect Sleep/Fatigue Medication Attention Deficits Disorders of Sleep Sleep disturbance Medication pain Disorder of mood Secondary to MS Pathologic Fatigue Fatigue Mental Physical Total Factors Causing Cognitive Symptoms MS lesions Mood/Affect Sleep/Fatigue Medication Attention Deficits Attention Deficit Disorder • Persistent pattern of inattention and hyperactivity-impulsivity or both. • Associated with volume differences in prefrontal cortex, and cerebellum • Prefrontal cortex regulates attention • Cerebellum connects directly to PFC Attention Deficits and Multiple Sclerosis • Attention is affected by individual differences in frontal cortex and cerebellum • Lesions often occur in these areas in MS • Attention deficits are a major complaint in MS • The combination of these factors in an individual can cause significant difficulties similar to those seen in ADD. Factors Causing Cognitive Symptoms MS lesions Mood/Affect Sleep/Fatigue Medication Attention Deficits Medication and Cognition • PAIN • Self medication • Recent steroid use- (Uttner et al, 2005) 30 patients with RRMS treated with standard and high doses of methylprednisolone for 5 days showed reversible impairment in declarative memory (CVLT) Medical Management of Cognitive Symptoms • • • • • Treat/control disease Mood/Affect Sleep/Fatigue Attention Deficits Medication Drug Studies • Betaseron- N=30, only one of 13 cognitive measures was improved compared with placebo at 2 and 4 years follow up • Avonex- N=166, improved information processing and memory compared with placebo at 2 years follow up Drug Studies • Copaxone- N=251, improvements occurred in neuropsychological test scores during 2 years of treatment regardless of whether patients were receiving Copaxone or placebo • Copaxone 10 yr- N=153, test of attention showed declining function for the group as a whole Drug Studies • Copaxone-10 yr ‘In general, cognitive worsening was associated with disease activity as measured by the relapse rate and changes in overall disability on the EDSS. Furthermore, ongoing disease activity and disability progression during the first 2 years predicted cognitive worsening during extended follow-up’ Mood and Affect • Appropriate and reactive? • Otherwise medication and psychotherapy • Treatment of pathological laughter and tears Antidepressants for MS • • • • • • SSRI’s Buproprion Effexor TCA’s Stimulants? Combination of therapy and medication is more effective than either alone Treatment for Pathological laughter and tears • • • • • Amitriptyline Levodopa Desipramine Fluoxetine Fluvoxamine Sleep/Fatigue • Review sleep hygiene • Sleep study • Medication only if necessary Medications for ADD • Stimulants- methylphenidate, amphetamine • Non-stimulants- atomoxetine • Alpha-agonists- clonindine, guanfacine • Buproprion • TCA’s • Modafinil Factors Causing Cognitive Symptoms MS lesions Mood/Affect Sleep/Fatigue Medication Attention Deficits