Neuropsychiatric Manifestations
of Multiple Sclerosis
•Presenter- Dr Bharath Reddy
•Moderator- Dr Keshava Pai
•Date- 12th August 2024
•Department of Psychiatry
•KMC Mangalore
Diseases of Myelin
• Dysmyelinating Disorders • Infectious
• Adrenoleukodystrophy • Progressive multifocal
• Metachromatic leukodystrophy leukoencephalopathy
• Krabbe disease • Toxic/Metabolic
• Alexander disease
• Carbon monoxide poisoning
• Canavan van Bogaert disease
• Vitamin B12 deficiency
• Pelizaeus-Merzbacher disease
• Mercury intoxication
• Phenylketonuria (Minamata disease)
• Demyelinating Disorders • Alcohol/tobacco amblyopia
• Autoimmune • Central pontine myelinolysis
• Marchiafava-Bignami
• Acute disseminated
syndrome
encephalomyelitis
• Acute hemorrhagic • Hypoxia
leukoencephalopathy • Radiation exposure
• Multiple sclerosis • Vascular Disorders
• Neuromyelitis optica
• Binswanger disease
Multiple Sclerosis
• Central Nervous System (CNS) Myelin Disorders:
• Demyelinating: Acquired, usually inflammatory.
• Dysmyelinating: Abnormal myelin formation, usually genetic.
• The most common immune-mediated inflammatory demyelinating disease of
the central nervous system is multiple sclerosis (MS).
Pathogenesis
Heterogeneous Pathologic Cause: Unknown. Widely Accepted
Disorder: Variable Mechanisms: Theory:
clinical and pathologic
features. Inflammation Begins as an inflammatory
Demyelination immune-mediated disorder with
autoreactive lymphocytes.
Axonal degeneration
Progresses to microglial activation
and chronic neurodegeneration.
Blood Brain Barrier
T helper 17-type (Th17)
cells
Tissue destruction
Epidemology
• Prevalence and Disability:
• MS is the most frequent cause of permanent disability in
young adults, aside from trauma.
• Affects more females than males.
• Female-to-male ratio increased from 1.4:1 (1955) to 2.3:1
(2000).
• Mean age – 28 to 31 years
Geographical Variation
Risk Factors
Gentic
1 AGE 3 Suseptibility 5 Vaccinations
• Strongest associations: • No positive
HLA-DRB1 locus, other non- association between
28-31years MHC susceptibility genes vaccines and MS.
(e.g., CD6, IL7R). • Some studies
• Vitamin D interaction with suggest protective
HLA-DRB1 might influence effects (e.g., tetanus
MS risk. vaccination).
Viral Infections
Common comorbid
autoimmune conditions: Sunlight and Vit
Psoriasis (7.7%), thyroid D
disease (6.4%).
Smoking
Autoimmun
e Environmental
2 4
Association Factors
s
Environmental Factors
• Viral Infections:
• Strong link between Epstein-Barr virus (EBV) and MS.
• Higher risk of MS after infectious mononucleosis.
• Sunlight and Vitamin D:
• Inverse relationship between sun exposure/vitamin D levels
and MS risk.
• Lower MS risk in individuals with higher vitamin D intake.
• Smoking:
• Tobacco smoking associated with increased MS risk and
disease progression.
MULTIPLE SCLEROSIS PHENOTYPES
• clearly defined • Secondary
attacks with full or progressive MS is
incomplete initial relapsing-
recovery remitting MS
gradual worsening
with or without
occasional relapses,
relapsing–
secondary
remitting
progressiv
disease
e disease
course
primary progressiv
progressiv e-
e disease relapsing
• steady progression
of disability from • acute attacks
the outset superimposed on
progressive decline
Ophthalmic Signs and Symptoms
• Retrobulbar
neuritis transient
Retrobulb
ar disturbance
• Antedating other
neuritis
manifestations by
many years.
Oculomot • Diplopia
or • Nystagmus
dysfunctio • Part of Brainstem
n syndrome
• Margus Gunn Pupil
Transient • Pallor in temporal
Visual loss
halves of optic disc
Motor Symptoms
Cerebell • Ataxia
ar signs • Intention tremors
• Exaggerated
tendon reflexes
• Absent abdominal
Reflexes reflex
• Extensor plantar
reflexes
• Joint position sense
• Dysarthria
Impaired • Impaired Vibration
sense
Brain MRI of
patient with
multiple sclerosis
demonstrating
Dawson fingers
•Axial (A) and sagittal (B)
MRI FLAIR images of the
brain demonstrate multiple,
ovoid periventricular lesions
(Dawson fingers) in a
patient with multiple
sclerosis.
•MRI: magnetic resonance
imaging; FLAIR: fluid-
attenuated inversion
recovery.
Neuropsychiatric Manifestations
Pseudobulb Bipolar
Depression Anxiety
ar affect Disorder
Cognitive
Psychosis Fatigue
Impairment
Depression In MS
Suicide rates are 2–7.5 times higher than the general
population
Depressio
n
Fatigue and PBA
pain Structural
changes in
brain MS
Overlapping symptoms –
Dx Confusion
daclizumab,
interferon-
alemtuzuma
b beta
natalizumab
Past history of
Disease modifying drugs depression- prophylactic
antidepressants
Depression in MS
Further Treatment
Considerations
First-Line
(CBT,
Initial Screening Pharmacological
Mindfulness,
Treatment (SSRIs)
Alternatives to
SSRIs)
Additional
Severe Cases
Treatments (Zinc,
(ECT)
Vitamin A)
[Link] Assessment
Use PHQ-9, Exclude and Check for Assess for past Mild depression:
HADS, BDI, or treat organic iatrogenic history of mania Consider CBT or
CES-D. causes. effects of or bipolar self-help.
medications. disorder.
[Link]-Line Pharmacological Treatment:
SSRIs (e.g., Titrate from a half
Consider SNRIs (e.g.
Sertraline, dose; monitor for
, Duloxetine,
Fluoxetine) due to serotonin syndrome
Venlafaxine) for co-
benign side-effect if using low-dose
morbid pain.
profile. TCAs for pain.
3. Further Treatment Considerations:
• CBT for moderate to severe depression; can be combined
with medication.
• Consider Mindfulness Training; avoid Omega-3 fatty acids.
• If SSRIs are not tolerated,
consider Moclobemide, Venlafaxine, Duloxetine,
or Mirtazapine (monitor for fatigue).
Anxiety
Anxiety appears to be linked to perceived lack of support, increased pain, fatigue, sleep
disturbance, depression, alcohol misuse and suicidal ideas.
The uncertainty of prognosis in MS is a major cause of anxiety in MS
SSRIs , Venlafaxine
BDZs
Buspirone and beta blockers
Pregabalin
CBT
Pseudobulbar affect
• Pathological Laughing or crying or Incongruence of affect
• small doses of TCAs, for example, amitriptyline or SSRIs, for example,
fluoxetine in MS.
• Citalopram, nortriptyline or sertraline have been investigated in people
with post-stroke PLC and shown reasonable efficacy and rapid response.
• Valproic acid may be effective.
• The combination of dextromethorphan and low-dose quinidine (DMq) is
effective.
• Dextromethorphan plus fluoxetine may show similar effects.
Bipolar Disorder
• The incidence of bipolar disorder can be as high as 13% in the MS
population compared with 1–6% in the general population.
• Sodium Valproate > Lithium
• Mania + psychosis low dose antipsychotics such as risperidone,
olanzapine and ziprasidone.
• Steroid induced mania Olanzapine
Psychosis
• Psychosis in MS: Affects 1.1% of the MS population; relatively uncommon
compared to other psychiatric disorders.
• Rare Presentation: Psychosis can rarely be the first symptom of MS.
• Treatment Options:
• Preferred Medications: Risperidone, Clozapine (low risk of extrapyramidal
symptoms).
• Possible Alternatives: Olanzapine, Aripiprazole, Quetiapine.
• Refractory Cases: Electroconvulsive therapy (ECT) may be used.
• MS Relapse: Psychosis may indicate a relapse; steroids may help but require close
supervision.
• THC Caution: Small risk of psychotic reactions in patients using THC-containing
formulations.
Cognitive Functions
• Cognitive Impairment in MS: Affects 40–65% of people with MS.
• Worsening Cognition: Medications like tizanidine, diazepam, and gabapentin can
worsen cognition.
• Improving Cognitive Function:
• Treatment of Sleep Issues, Depression, and Fatigue: Can enhance
cognitive function based on clinical case studies.
• Medications:
• Donepezil: Two small trials showed moderate efficacy; a larger study found no
effect.
• Memantine: Weak supporting data.
• Overall Efficacy: No symptomatic treatment has shown consistent efficacy.
• Promising Treatments: Disease-modifying agents offer greater promise.
References
• Silveira C, Guedes R, Maia D, Curral R, Coelho R. Neuropsychiatric symptoms of multiple
sclerosis: state of the art. Psychiatry investigation. 2019 Dec;16(12):877.
• Murphy R, O’Donoghue S, Counihan T, McDonald C, Calabresi PA, Ahmed MA, Kaplin A,
Hallahan B. Neuropsychiatric syndromes of multiple sclerosis. Journal of Neurology,
Neurosurgery & Psychiatry. 2017 Aug 1;88(8):697-708.
• VAILLANT GE. Normality and Mental Health: Ch. 3.6 of Kaplan and Sadock's
Comprehensive Textbook of Psychiatry. Sadock, B., Sadock, V. & Ruiz, P. Eds.(2017)©
Wolters Kluwer Health.
• World Health Organization. The ICD-10 classification of mental and behavioural disorders:
clinical descriptions and diagnostic guidelines. World Health Organization; 1992.
• American Psychiatric Association DS, American Psychiatric Association. Diagnostic and
statistical manual of mental disorders: DSM-5. Washington, DC: American psychiatric
association; 2013 May 22.
• Tasman A, Kay J, Lieberman JA, First MB, Riba M, editors. Psychiatry, 2 volume set. John
Wiley & Sons; 2015 Mar 30.
