Disclosures Re cent Advances in Neurology I receive grant support - - PowerPoint PPT Presentation

2/10/2017 1

Recent Advances in Neurology

Difficult Diagnosis “Neck Spasms”

Nicholas Galifianakis, MD, MPH

Assistant Professor of Neurology UCSF Movement Disorders and Neuromodulation Center

Disclosures

I receive grant support from:

• National Institutes of Health (NIH)
• Patient Centered Outcomes Research Institude (PCORI)
• Boston Scientific Corp.
• International Parkinson and Movement Disorders Society
• Edmond J. Safra Foundation (Educational Grant)

History (1)

• 45 year-old RH man
• Referral: involuntary “neck spasms”
• Chief complaint: “spasms” of left leg, left arm, and

head/neck x 10 years

• Childhood (age 8-10): walked “pigeon-toed”, but

remained athletic through high school and later

• 1992 (age 27): arm posturing noted by friends,

but not bothersome, still worked as contractor

• 2000 (age 35): left foot inversion, affecting gait,

still worked as high school basketball coach

• 2010 (age 45, referral): more progressive and
• disabling. Having trouble at work, gait difficult.

History (2)

• PMH: Arthritis, Depression, otherwise healthy
• PSH: Cervical “spine surgery” after “bone spur

found compressing nerve” on MRI. (Relieved shoulder and neck pain, but not the abnormal movements).

• Medications: Duloxetine, Citalopram, Tramadol,

Trihexyphenidyl 2mg QD, Lorazepam 5mg BID, Carbidopa/Levodopa “CR” 25/100 BID

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History (3)

• ROS: (+)Gait disturbance, occasional falls.
• No cognitive, behavioral, autonomic complaints. No

sensory complaints (except painful muscle spasms. No weakness, no change in speech/swallowing).

• SH: Married with 5 adopted children. College

graduate, now working as substitute teacher, basketball coach. No substance use/exposure.

• FH: younger brother (age 41) recently mentioned

stiffness and abnormal movements on one side. English/German ancestry.

Examination (1)

• General examination was normal.
• On neurologic examination:

Mental status was normal. Memory, language,

attention, naming, and visuospatial function were normal.

Cranial nerve examination was normal, with

normal voice and facial expression.

Sensation and coordination were normal. DTRs brisk throughout, including crossed adductors,

but no Babinski sign.

Examination (2)

• Movement Disorders Examination:

Tone was minimally increased in the neck, left arm

and leg (only brought out with distraction).

No tremor at rest, postures, or actions. Rapid repetitive movements (finger taps, hand

movements, heel stomps)

Possible mild bradykinesia - somewhat difficult to

interpret whether just a consequence of abnormal movement

Examination (3)

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Question #1

The predominant phenomenology of abnormal movements seen in this examination is most consistent with:

A.

Chorea

B.

Dyskinesia

C.

Parkinsonism

D.

Dystonia

C h

• r

e a D y s k i n e s i a P a r k i n s

• n

i s m D y s t

• n

i a

1% 86% 4% 9%

Dystonia

• Movement disorder

characterized by sustained/intermittent muscular contractions causing abnormal repetitive movements, postures, or both

• Typically patterned,

twisting, and may be tremulous

• Often initiated or worsened

by voluntary action, a/w

• verflow muscle activation

Dystonia Consensus Update (Jinnah, Delong, Hallett. Movement Disorders. 2013)

“New” Dystonia Classification

• Axis 1 – Clinical features

Age of Onset (infancy, thru late adult) Body distribution (focal, segmental, generalized) Temporal pattern (static, progressive course) Isolated or Combined w/other movement disorder

(e.g. parkinsonism, myoclonus, etc..)

Our Case: Axis 1: Childhood onset, generalized,

progressive, isolated vs combined dystonia.

“New” Dystonia Classification

• Axis 2 – Etiology

Inherited

DYT genes Familial Parkinsonism: YOPD/Juvenile PD Other: Wilson’s disease, Familial BG calcifications,

HD, SCA, NBIA/PKAN, Ataxia-Teleangiectasia, Neuroacanthocytosis, Lesch-Nyhan

Acquired

Nonfamilial Parkinsonism: PD, MSA, CBD, PSP… Tardive syndromes (DRBA exposure), toxic Other: Brain injury, ischemic, metabolic …

Idiopathic

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Prior Work-up/Mgmt

• Metabolic labs, Thyroid labs, vitamin E level,

ceruloplasmin, and anti-GAD antibodies all normal.

• MRI Brain normal
• MRI cervical spine showed a “bone spur

compressing a nerve”

• (*) Levodopa 25/100 BID “helped”, but not clear

whether trihexyphenidyl, tramadol, lorazepam

Prior Work-up/Mgmt

• Levodopa responsive?

Do symptoms worsen right before next dose, or if

you miss a dose?”

“Not sure”

Is there a particular time of day when you are at your

worst?

“Yes, in the morning…” “Wake up with legs very stiff, and bent over” “Straighten up” after morning meds.

Differential Diagnosis (Axis 2 – Etiology)

• Our Case: Axis 1: Childhood onset, generalized,

progressive, isolated vs combined...

• Inherited Dystonia (“Primary”)
• Acquired Dystonia (“Secondary”)
• Dopamine-responsive Dystonia (DRD)
• Young-onset Parkinson’s Disease (YOPD)

Differential Dx

Familial dystonia (DYT genes)

• DYT1 most common:

Most commonly presents in childhood, legs Usually becomes generalized over course of

childhood/adolescence

• Other DYTs: a diverse group, some a/w

Parkinsonism, Ataxia, rarely dopamine responsive

DYT3 (Lubag) DYT5 (Segawa = DRD)

Other acquired (brain injury, tardive, ischemic, etc…)

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Differential Dx: DRD

Dopamine-Responsive Dystonia (DRD)

• Group of familial disorders with mutations in the

enzymatic pathway of dopamine synthesis

• DYT5: GTP Cyclohydrolase (GCH1), (Segawa

Syndrome), Tyrosine Hydroxylase (TH)

• Onset in Childhood
• Diurnal pattern of sensitivity (best in a.m.)
• Very responsive to low-dose Levodopa
• Not neurodegenerative
• Negative genetic tests do NOT exclude DRD

Differential Dx: YOPD

• Young onset Parkinson’s disease (YOPD)
• Symptom onset <40 years old
• Parkin, PINK1, LRRK2 most common genes found

in this group (but still don’t account for majority)

• More tremor, more dystonic cramps/posturing
• Slower progression
• Earlier dyskinesia
• Better response to meds and DBS

Question #2

All of the following would be helpful in distinguishing Dopamine-Responsive Dystonia (DRD) and other dystonias from Neurodegenerative Parkinsonism (PD) EXCEPT:

A.

Response to Levodopa (e.g. On/off testing)

B.

Dopamine transporter (DAT) Scan

C.

Response to Botulinum toxin injection

D.

Genetic testing (DRD + Familial PD panels)

R e s p

• n

s e t

• L

e v

• d
• p

a ( e . . . D

• p

a m i n e t r a n s p

• r

t e r ( . . . R e s p

• n

s e t

• B
• t

u l i n u m t . . . G e n e t i c t e s t i n g ( D R D + F a . . .

9% 5% 78% 9%

Question #3

Which of the following is the most likely diagnosis at this time?

A.

Dystonic Cerebral Palsy

B.

Young Onset Parkinson’s disease

C.

Dopamine-Responsive Dystonia (Segawa)

D.

DYT-3 Dystonia (Lubag)

Dystonic Cerebral Palsy Young Onset Parkinson’s ... Dopamine-Responsive Dy... DYT-3 Dystonia (Lubag)

3% 25% 51% 21%

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Diagnosis

• Genetic testing: DRD and PD panels revealed …
• DYT1, DYT5 (GCH1, TH), PINK1 (PARK6),

LRRK2 (PARK8) = Negative

• Parkin (PARK2) (+)

Predicted disease-associated mutations:

Homozygous Deletion of Exon 4 Deletion in Exon 1

Potential adjacent disease-associated mutations

(deletions in exons 2, 3, 5)

• Diagnosis: Parkin (PARK2)(+) YOPD

PARK2 (Parkin) YOPD

• Found in 1998, several Japanese families (REF)
• 6p27, deletions in 1+ exons
• #1 cause of YOPD/EOPD (onset < 40, mean 27)
• #1 cause (and majority) of AR PD
• Diurnal fluctuations, improvement after sleep
• Initially mild, slow progression, rare ANS/Cog.
• Very responsive to Levodopa
• Leg dystonia very common (>90%)
• Pathology: Absence of Lewy Bodies

Case: Clinical Course

• Botulinum toxin: “90%” relief of pain/laterocollis:

Left Splenius, Levator Scap, SCM, Trapz (200 units)

• Dramatic response to levodopa, however,

developed “motor complications” wearing off Q2hrs, bothersome dyskinesia

• 2012 Disability: eval for DBS, minimal non-motor
• nce depression treated, MOCA 29/30.
• Goals: Improve fluctuations, dyskinesia, Off sx
• 2013 bilateral GPi-DBS
• 2016 continues to do extremely well

Summary: DRD vs YOPD

• Similarities: both prominent dystonia early (esp. in

legs), very responsive to Levodopa, better w/sleep

• Differences:

DRD almost always clear onset in childhood YOPD: parkinsonism on exam (but difficult early

when mild rigidity/brady, and confounding dystonia).

• YOPD frequently misdiagnosed as ET or Dystonia

Not expected in younger population Postural component of tremor Long period of time when Dystonia predominant sx

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THANK YOU.