ASSOCIATION OF BRITISH NEUROLOGISTS

ACUTE NEUROLOGY BOOT CAMP 2020

Wednesday 17th June

Dr Aisling Carr

NHNN, London

Acute Neuromuscular Weakness

ACUTE NEUROMUSCULAR WEAKNESSDr Aisling Carr

Consultant Neurologist

CNMD, NHNN

aisling.carr@nhs.net

ALL THE CMT’S………..

NEUROMUSCULAR BOOTCAMP

Neuromuscular respiratory failure

Physiology

• Lungs, respiratory drive, respiratory muscles• Diaphragm: 70%• Inspiratory: SCM, intercostal, scalene• Expiratory: abdominal wall, intercostal

• Respiratory failure: 25-30% of normal

Pathophysiology• ↓functional residual capacity

• ↑work of breathing• ↓gas exchange

• More susceptible to subtle changes

NEUROMUSCULAR BOOTCAMP

Neuromuscular respiratory failure

Physiology

• Lungs, respiratory drive, respiratory muscles• Diaphragm: 70%• Inspiratory: SCM, intercostal, scalene• Expiratory: abdominal wall, intercostal

• Respiratory failure: 25-30% of normal

Pathophysiology• ↓functional residual capacity

• ↑work of breathing• ↓gas exchange

• More susceptible to subtle changes

Investigations• FVC<20ml/Kg • ↓15-20% on lying • MIP<80cm H20• SNIP <70cm H20• Peak cough flow <160-200L/min• ABG• CXR• Overnight oximetry

NEUROMUSCULAR BOOTCAMP

Acute neuromuscular respiratory failure

ICU admission: I&V

• Patient anxiety, respiratory effort and HR

• FVC<1L or <1.5ml/kg

• ↓FVC >50%• Bulbar weakness

NEUROMUSCULAR BOOTCAMP

Acute-on-chronic neuromuscular respiratory failure

NIV

• Confusion, sedation

• Hypercapnia (PaCO2 >6kPa)

• Hypoxia

NEUROMUSCULAR BOOTCAMP

Top three neuromuscular OOH scenarios

•Essential clinical assessment

•Management

•Molecular mechanisms

CASE 1

• 25yr old

• 4 days earlier lower back pain

• 3 days of tingling in feet

• Past 2 days feels weak in his legs

• Today clumsy in his hands

• Fall in the shower when washing hair

CASE 1

• 25yr old

• 4 days earlier lower back pain

• 3 days of tingling in feet

• Past 2 days feels weak in his legs

• Today clumsy in his hands

• Fall in the shower when washing hair

Normal cranial nerves

Normal speech

Grade 4 in hands

HF 4 ADF 4 b/l

Areflexia

Impaired JPS to ankle

PP : lower abdomen

Romberg positive

UMN LMN

↑tone

No wasting

↑reflexes

↑plantars

↓tone

Muscle wasting

↓reflexes

↓plantars

Brain Cord Nerve NMJ Muscle

Root Neuropathy Mononeuro

pathy

Distribution Hemi-body Symmetrical asymme

trical

Symmetrical patchy Ocular,

bulbar,

limb

girdle

Symmetric

al

Pattern of

weakness

Pyramidal

pattern

Pyramidal

pattern

Myotom

al

pattern

Length

dependent

Patchy Fatiguab

le

Limb girdle

Gait Circumductin

g gait

Spastic diplegia Foot drop/

high

steppage

asymmetric

al

Waddle

/

trendele

nberg

trendelenb

erg

Sensory

involvement

Contralateral

sensory

inattention

Truncal sensory

level

Dermat

omal

Length

dependent

Correspon

ding

No No

UMN LMN

↑tone

No wasting

↑reflexes

↑plantars

↓tone

Muscle wasting

↓reflexes

↓plantars

Brain Cord Nerve NMJ Muscle

Root Neuropathy Mononeuro

pathy

Distribution Hemi-body Symmetrical asymme

trical

Symmetrical patchy Ocular,

bulbar,

limb

girdle

Symmetric

al

Pattern of

weakness

Pyramidal

pattern

Pyramidal

pattern

Myotom

al

pattern

Length

dependent

Patchy Fatiguab

le

Limb girdle

Gait Circumductin

g gait

Spastic diplegia Foot drop/

high

steppage

asymmetric

al

Waddle

/

trendele

nberg

trendelenb

erg

Sensory

involvement

Contralateral

sensory

inattention

Truncal sensory

level

Dermat

omal

Length

dependent

Correspon

ding

No No

Case 1: Anatomical localisation?/mechanism?

GUILLAIN-BARRE SYNDROME

IR=1/100,000 per year

Nadir @ 2-4 weeks

>8weeks suggests CIDP

20-25% require respiratory +/- cardiovascular support

5% mortality rate

Subacute onset, monophasic, immune-mediated polyradiculoneuropathies

Demyelinating and axonal forms

GBS PATHOGENESIS

GBS PATHOGENESIS

Molecular mimicry

Associated pathogens

C.jejuni

CMV

EBV

M.pneumoniae

H.influenzae

HEV

Zika virus

Vaccinations

Antibodies:

GM1

GD1a

GQ1b

Patterns of weakness in Guillain-Barré syndrome (GBS) and

Miller Fisher syndrome and their subtypes.

Benjamin R Wakerley, and Nobuhiro Yuki Pract Neurol

2015;15:90-99

©2015 by BMJ Publishing Group Ltd

The GB Syndromes

AIDP Acute inflammatory demyelinating

polyradiculoneuropathy.

AMAN - Acute motor axonal neuropathy .

AMSAN - Acute motor and sensory axonal neuropathy .

Pharyngeal- Cervical Brachial Variant

Miller-Fisher Syndrome (Opthalmoplegia, Ataxia and Areflexia)

Bickerstaffs (CNS involvement- low GCS/brainstem)

Pure Sensory Neuropathy.

Acute Pandysautonomia.

Acute or sub acute, monophasic neuropathy.

Acute :- Peak disability by 4 weeks.

Antecedent “trigger”

Areflexia (10% can have retained or even brisk reflexes)

CSF “albuminocytologic dissociation”

Generally spontaneous recovery occurs

Commonalities…..

INVESTIGATION/ DIAGNOSIS

Clinical presentation

Neurophysiology

CSF- albuminocytological dissociation

Central Imaging if atypical presentation

In acute setting- Clinical presentation and CSF (albuminocytological dissociation)

INVESTIGATION/ DIAGNOSIS

Clinical presentation

Neurophysiology

CSF

Normal Central Imaging

Exclude mimics

Variants and Mimics of Guillain Barré SyndromeLevin, Kerry H. MDThe Neurologist: March 2004 -Volume

INVESTIGATION/ DIAGNOSIS

Neurophysiology

Delayed F-waves

Temporal dispersion

Conduction block

MANAGEMENT OF GBS

Who? Mild- mobile independently- not treated Yet at 6 months up to 38% patients may have hand function problems

When? “Time is Nerve”, probably optimal to treat early

With what IVIG and PLEX are equitable in the trails. IVIG preferred

What if they aren’t getting better? Mmmmmmm

MEGOS

The role of steroids? Early trials suggested higher mortality in GBS- yet clear benefit in SIDP, CIDP and in GBS models

Use if disability continuing beyond 4 weeks

Check Neurofascin and contactin antibodies

PLEX?

Second IVIg??......

Non-responders?

IGOS 2ND IVIG?

Walgaard et al. Second IVIg Course in Guillain-Barré Syndrome Patients with PoorPrognosis (SID-GBS) Second IVIg Dose in Guillain-Barré Syndrome;Double-blind Randomized Controlled TrialJPNS Suppl 2019.

The role of steroids?

Early trials suggested higher mortality in GBS- yet clear benefit in SIDP, CIDP and in GBS models

Use if disability continuing beyond 4 weeks

Check Neurofascin and contactin antibodies

PLEX?

Second IVIg??......

Complement inhibitors: GBS-JET phase 3 trial underway

Non-responders?

OTHER ASPECTS TO MANAGEMENT

SIADH

Thromboembolism

Labile BP- failure of autoregulation causing PRES

Cardiac Monitoring for tachy-brady- PPM insertion may be required

Gut

@12 months- over 60% independently ambulate

OUTCOME

GBS

GBS

56 yr old male

Previously fit and well

4 week history of Diplopia- horizontal Variable through the day Struggling with drinks- leaking from mouth Slurred and low volume speech

Admitted to hospital

?

CASE 2

Whilst in hospital Weakness of neck- head drop

Weakness of arms: SAD/ WE, FE)

Difficulty breathing, but CXR normal-taken to the ICU Low FVC, VC and borderline PEFR

Needed ICU as tiring, confused

Noted to using accessory muscles and accessory muscle use

Exam Ptosis

Complex ophthalmoplegia

Facial weakness

Fatiguable dysarthria

Neck flex/ext weakness

Fatiguable UL weakness

Intact reflexes

Normal sensory exam

MRI Brain normal

UMN LMN

↑tone

No wasting

↑reflexes

↑plantars

↓tone

Muscle wasting

↓reflexes

↓plantars

Brain Cord Nerve NMJ Muscle

Root Neuropathy Mononeuro

pathy

Distribution Hemi-body Symmetrical asymme

trical

Symmetrical patchy Ocular,

bulbar,

limb

girdle

Symmetric

al

Pattern of

weakness

Pyramidal

pattern

Pyramidal

pattern

Myotom

al

pattern

Length

dependent

Patchy Fatiguab

le

Limb girdle

Gait Circumductin

g gait

Spastic diplegia Foot drop/

high

steppage

asymmetric

al

Waddle

/

trendele

nberg

trendelenb

erg

Sensory

involvement

Contralateral

sensory

inattention

Truncal sensory

level

Dermat

omal

Length

dependent

Correspon

ding

No No

INVESTIGATION

NCS/EMG: Normal

RNS/SFEMG: confirms a junctionopathy

Acetylcholine receptor ab positive(MuSK if bulbar predominance)

Ct Thorax confirms a enlarged Thymus Gland

Diagnosis: Myasthenia Gravis

NMJ transmission and failure

NEUROPHYSIOLOGY

10 % decrement 1st: 5th positive• 65-80% Generalised• 50% Ocular

Repetitive nerve stimulation Single fibre EMG

Normal jitter < 35µsec.

Abnormal

94% Generalised MG.

80% Ocular MG.

Also abnormal in MND, Myopathy and Neuropathy.

DIFFERENTIAL DIAGNOSIS

Brainstem Pupils Bulbar vs pseudobulbar/cerebellar Bladder/Bowel

Peripheral Nerve (GBS etc) Areflexia Pupils Wasting

Anterior Horn Eyes not involved Fascics/Wasting

Muscle CK Ocular /Facial not involved

All lack fatiguability and diurnal variation

MG EPIDEMIOLOGY

IR: 14/million per year

PR: 150/million0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 >80

0

25

50

75 Thymoma MG

Non-thymoma MG

age groups (years)

nu

mb

er

of

ca

se

s

00

50

100

150

Male

Female

0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 >80

EOMG LOMG

age group (years)

IR (

cases p

er

mil

lio

n p

ers

on

-years

)

AS Carr. Actual world epidemiology of Myasthenia Gravis (Chapter

2). In Mineo TC, editor. Novel Challenges in Myasthenia Gravis.

Nova Science Publishers, Inc.: 2015;

MG EPIDEMIOLOGY

IR: 14/million per year

PR: 150/million0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 >80

0

25

50

75 Thymoma MG

Non-thymoma MG

age groups (years)

nu

mb

er

of

ca

se

s

00

50

100

150

Male

Female

0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 >80

EOMG LOMG

age group (years)

IR (

cases p

er

mil

lio

n p

ers

on

-years

)

MANAGEMENT

A patient should be managed in hospital for significant bulbar symptoms, low vital capacity, respiratory symptoms or progressive deterioration.

Assessment by speech and language therapist to advise on swallowing is mandatory.

Regular assessment of vital capacity is mandatory.

•IVIg (2g/kg/3-5 days) or PLEX

•Commence oral steroids

•Pyridostigmine

Sussman J,Farrugia ME, Maddison P,et al. Pract Neurol 2015;15:199–206.

MANAGEMENT

A patient should be managed in hospital for significant bulbar symptoms, low vital capacity, respiratory symptoms or progressive deterioration.

Assessment by speech and language therapist to advise on swallowing is mandatory.

Regular assessment of vital capacity is mandatory.

•IVIg (1g/kg/3-5 days) or PLEX

•Commence oral steroids

•Pyridostigmine

•RCT: Rozanolixizumab

Sussman J,Farrugia ME, Maddison P,et al. Pract Neurol 2015;15:199–206.

MANAGEMENT

A patient should be managed in hospital for significant bulbar symptoms, low vital capacity, respiratory symptoms or progressive deterioration.

Assessment by speech and language therapist to advise on swallowing is mandatory.

Regular assessment of vital capacity is mandatory.

•IVIg (2g/kg/3-5 days) or PLEX

•Commence oral steroids

•Pyridostigmine

•RCT: Rozanolixizumab

Sussman J,Farrugia ME, Maddison P,et al. Pract Neurol 2015;15:199–206.

GBS

MG

GBS

MG Acute on Chronic

GBS

MG Acute on Chronic

De novo NMRF:

• MND

• MG

• Adult onset acid maltase deficiency (Pompe’s)

• Mitochondrial myopathy

• Sporadic late-onset nemaline myopathy

• colchicine myopathy

CHRONIC NMRF

CHRONIC NMRF

• Cardiorespiratory surveillance• Emergency care plan• End of life discussion

ASSOCIATION OF BRITISH NEUROLOGISTSACUTE NEUROLOGY BOOT CAMP 2020

Week 2

15 June 7 – 8 pm Stroke - Dr Akram Hosseini, Nottingham

16 June 7 – 8 pm The Dizzy Patient - Dr Diego Kaski, London

17 June 7 – 8 pmAcute neuromuscular weakness - Dr Aisling Carr,

London

18 June 7 – 8 pmSurviving your first year as registrar - Dr Alex Foulkes,

London

Association of British Neurologists, Ormond House, 27 Boswell Street, London WC1N 3JZ

Email: info@abn.org.uk. Telephone: 02074054060