Title: Cognitive Dysfunction in Multiple Sclerosis Stavra Romas, MD Neurologist, Cognitive Division IMSMP
1Cognitive Dysfunction in Multiple
SclerosisStavra Romas, MDNeurologist,
Cognitive DivisionIMSMP
2Cognitive Symptoms in MS
- What is the person experiencing?
- What is causing the complaints?
- What can we do about it in terms of medical
management?
3Overview of Cognitive Symptoms
- 40-50 have cognitive symptoms
- 10 meet criteria for dementia
- Cognitive symptoms can occur early
- Information doesnt increase fears (Segal et al.,
2006) - Screening is important
4Assessment 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
5Factors Causing Cognitive Symptoms
6How MS lesions Affect Cognition
- Lesion load
- Atrophy
- Normal appearing white matter
- Other factors?
7Lesion 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)
8Lesion 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)
9Brain 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.
10(No Transcript)
11MRI Findings Never Explain the Whole Picture
- NAWM?
- Temporal course or age at onset?
- Other factors?
12Factors Causing Cognitive Symptoms
13Disorders of Mood and Affect
- Euphoria/lability
- Pseudobulbar symptoms
- Depression
- Anxiety
- Bipolar Symptoms
- Psychotic Symptoms
14Neuropsychiatric 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
15Neuropsychiatric 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)
16Factors Causing Cognitive Symptoms
17Disorders of Sleep
18Pathologic Fatigue
19Factors Causing Cognitive Symptoms
20Attention 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
21Attention 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.
22Factors Causing Cognitive Symptoms
23Medication 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)
24Medical Management of Cognitive Symptoms
- Treat/control disease
- Mood/Affect
- Sleep/Fatigue
- Attention Deficits
- Medication
25Drug Studies
- Betaseron- N30, only one of 13 cognitive
measures was improved compared with placebo at 2
and 4 years follow up - Avonex- N166, improved information processing
and memory compared with placebo at 2 years
follow up
26Drug Studies
- Copaxone- N251, improvements occurred in
neuropsychological test scores during 2 years of
treatment regardless of whether patients were
receiving Copaxone or placebo - Copaxone 10 yr- N153, test of attention showed
declining function for the group as a whole
27Drug 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
28Mood and Affect
- Appropriate and reactive?
- Otherwise medication and psychotherapy
- Treatment of pathological laughter and tears
29Antidepressants for MS
- SSRIs
- Buproprion
- Effexor
- TCAs
- Stimulants?
- Combination of therapy and medication is more
effective than either alone
30Treatment for Pathological laughter and tears
- Amitriptyline
- Levodopa
- Desipramine
- Fluoxetine
- Fluvoxamine
31Sleep/Fatigue
- Review sleep hygiene
- Sleep study
- Medication only if necessary
32Medications for ADD
- Stimulants- methylphenidate, amphetamine
- Non-stimulants- atomoxetine
- Alpha-agonists- clonindine, guanfacine
- Buproprion
- TCAs
- Modafinil
33Factors Causing Cognitive Symptoms