Neuro2: Huntington's Disease

Front 1

Genetics of Huntington's

Back 1

AD inheritance, c4 short arm CAG repeats, 40 is the cutoff, non mutated copy is 10-20 range. KNOW 4 (chromosome), 40 (repeats), CAG

If below 30s probably won't die of it, if in 40s will get later, if have 50s might even get juvenile

Anticipation when inherited from father (expansion of gene, expands more from father), if from mother more likely to get same # of repeats

100% penetrant, NO ASYMPTOMATIC CARRIERS

At any time 2/3 of gene carriers are not yet affected

Front 2

Worldwide localization of Huntington's

Back 2

US, Northern Europe, Australia

Highest in world is in Lake Maracaibo in Venezuela. 40-50% of the population

Front 3

Brain changes in HD

Back 3

Selective brain atrophy, accumulation of insoluble huntingtin protein, neurochemical changes

Caudate nucleus atrophy

Front 4

Clinical Presentation of HD, Onset, Triad, Course, Juvenile HD

Back 4

Onset 30-50s, loss of prime productivity years and many pts have had children

Some correlation between repeat length and symptom onset/severity

Triad: Motor chorea (gait problems, speech, swallowing, coordination), Cognitive disability (executive dysfunction progressing to dementia), Psychiatric (depression, ocd, impulsivity, suicide risk, irritability, apathy, personality change)

Course: Varies but 10-30 years from onset to death

Juvenile cases is less chorea and more parkinsonian and has higher repeats. <20 yr survival

Front 5

Triad of HD

Back 5

Motor chorea (gait problems, speech, swallowing, coordination), can have tics, dystonia, slowing of smooth pursuit/saccades

Cognitive disability (executive dysfunction progressing to dementia),

Psychiatric (depression, ocd, impulsivity, suicide risk, irritability, apathy, personality change)

Front 6

Most common presenting symptom of HD

Back 6

Motor chorea (gait problems, speech, swallowing, coordination), can have tics, dystonia, slowing of smooth pursuit/saccades

Front 7

Diagnosis of HD

Back 7

NO CLINICAL DIAGNOSTIC CRITERIA (Unlike parkinson's)

Positive gene test is the diagnosis

Front 8

When to order HD gene test, caveats

Back 8

If

a) No FHx but chorea and suspect (just test)

b) Positive FHx and symptomatic (just test)

c) Positive FHx but asymptomatic (test AND pre/post test genetic counseling)

However, asymptomatic means NO motor symptoms

Testing for pts under 18 not done

KNOW THIS, symptomatic no counseling needed, asymptomatic needs counseling

Front 9

Genetic Counseling Process in HD

Back 9

Neuro exam to confirm to HD motor symptoms

Visits with neuropsychologist to determine readiness to receive results

Visits with geneticist to review ramifications of testing, blood drawn at last visit

Confidential, nothing filed into official medical record

At UAB free except cost of test to pt

Front 10

Treatment of HD Motor symptoms

Chorea, focal dystonias, parkinsonism, & refractory chorea, tics or dystonia

Back 10

Chorea - Tetrabenazine (NOT quetiapine/clozapine)

Focal dystonias - botulinum toxin

Parkinsonism - Levodopa

Refractory chorea, tics, dystonia - DBS

Front 11

Key structure loss in Huntington's Disesae

Back 11

Loss of Caudate neurons involved in the indirect pathway running from Caudate to GPe. This is a GABAergic inhibitory interneuron. Less inhibition on GPe, GPe becomes more active. It's inhibitory so it inhibits STN, It is excitive and less excitaton of GPi. GPi is inhibitory so less inhibition of thalamus VL/VA so more movement

Front 12

Tetrabenazine use, ASE

Back 12

Reduce chorea movements in HD

ASE: can cause anxiety, akathisia so a high dose SSRI may be preferred

Front 13

Treating psychiatric symptoms in HD, depressed mood vs apathy

Back 13

Treat even to just reduce symptoms

Depressed mood - for sleep disorders look for trigger, Responds well to SSRIs. Want to reduce risk of impulsivity and suicide

Apathy - diminished motivation but NO sad mood, Bupropion, stimulants

Front 14

Treatment of Psychiatric HD symptoms anxiety, OCD, Irritability/impulsivity

Back 14

Anxiety - TBZ can cause, HIGH DOSE SSRI

OCD - not true OCD since lack of insight, HIGH DOSE SSRI, clomipramine

Irritability/impulsivity - SSRI, antipsychotics (esp. nursing home), mood stabilizers

Basically high dose SSRIs for psychiatric Sx

Front 15

Treatment for Cognitive Symptoms of HD

Back 15

Cholinesterase inhibitors and Memantine NO BENEFIT

Encourage to use non-pharmacologic aids

Front 16

Affected cognitive domains in HD

Back 16

Attention, executive function, psychomotor speed, working memory, emotion recognition

Front 17

GROSS PATHOLOGY PICTURE TO KNOW

Back 17

SELECTIVE ATROPHY OF CAUDATE NUCLEUS

Rest of brain isn't normal, generalized atrophy but selective caudate atrophy alters shape of ventricles (can see on MRI too, not diagnostic though)