AN INTERESTING CASE OF DIPLOPIA

PROF. P. VIJAYARAGHAVAN’S UNIT(M4 UNIT)

DR. STALIN

Malliga, a 48 year old female presented with

c/o Inability to close the Left eye – 3 days Redness of Left eye - 3 days

Double vision - 3 days Difficulty in swallowing - 3 days

H/O Present illness Patient was apparently normal 3 days ago, on

waking up in the morning she found her left eye was red on looking into the mirror. While attempting to close she was unable to close the Left eye.

She had double vision, which was maximum on looking to the right. On closing one eye double vision disappeared. Relatives noted inward (nasal) deviation of right eye ball.

She was also having difficulty in swallowing both for solid and liquids, however the symptoms were mild and despite it she was able to eat normally at the time of admission. She had mild slurring of speech

Two days later she was unable to stand from squatting position without support. However gripping of slippers were normal and there was no stiffness of limbs.

She also has un-steadiness while walking. She was able to feel the warmth of tap

water and able to feel her clothes. No difficulty in using her upper extremities. No h/o bladder and bowel disturbances. No h/o breathing difficulty.

No symptoms ascribable to higher mental function abnormality.

No h/o dizziness on standing. h/o cough with expectoration. No h/o fever prior to the episode. No h/o diarrhea. No h/o drugs, injections.

PAST HISTORY;

Known T2DM for past 3 years on OHA and recently started on insulin.

She was admitted for increased blood sugar two weeks ago and was started on insulin at a private hospital.

Not a known SHT/ COPD/PT No h/o similar complaints in the past

PERSONAL HISTORY

Mixed dietNo addictions

FAMILY HISTORY

No family history of neurological complaints.

No h/o contact with a known tuberculosis patient.

GENERAL EXAMINATION

Pt conscious , oriented to time, place, personAfebrileNo pallorNot ictericNo cyanosisNo clubbingNo pedal edemaNo lymphadenopathy

Red eye (left exposure keratitis) + Pupil bilateral 3mm reacting to light Thyroid swelling + No neuro-cutaneous markersVITALS PR-84/min, Regular rhythm BP 120/90 mm Hg RR -16/min JVP- normal

Systemic examination

CVS : S1,S2 heard no murmurs RS : NVBS no added sounds P/A : Soft no organomegaly No free fluid

CNS EXAMINATION

Higher mental function; Conscious, Oriented to time place person Memory recent and remote- normal Speech- mild dysarthria

MOTOR SYSTEMRIGHT LEFT

UPPER LIMB LOWER LIMB UPPER LIMB LOWER LIMB

BULK NORMAL NORMAL NORMAL NORMAL

TONE NORMAL NORMAL NORMAL NORMAL

POWER 5/54/5

(PROX>DIST)5/5

4/5(PROX>DIST)

DEEP TENDON REFLEXES

+ ++ + ++

PLANTAR FLEXOR FLEXOR

CRANIAL NERVES;

1 - Normal 2 - COLOUR, FIELD OF VISION - NORMAL

PUPIL 3mm REACTING TO LIGHT 3,4,6- RT Abduction impaired RT lateral rectus palsy,

Dolls eye reflex Rt Abduction impaired 5- Normal 7- Left LMN type facial muscle weakness 8- Normal 9,10 - Gag reflex – B/L absent 11- B/L shoulder shrugging, head turning

minimally weak 12- Normal

Right abducent palsy

Lool left

Look

straight

Look right

Bells phenomenon

Sensory systemRIGHT LEFT

UL LL UL LL

PAIN NORMAL NORMAL

TEMPERATURE NORMAL NORMAL

TOUCH NORMAL NORMAL

VIBRATION NORMAL NORMAL

POSITION NORMAL NORMAL

CORTICAL SENSATION - NORMALROMBERG'S – UNSTEADINESS BOTH EYES OPEN & CLOSED

CEREBELLAR SIGNS FINGER NOSE TEST – NORMAL HEEL SHIN KNEE TEST – NORMAL NO DYSDIADOCHOKINESIA, GAIT – ATAXIA+ (TANDEM WALKING -

IMPAIRED) SPINE AND CRANIUM - NORMAL MENINGIAL SIGNS - NIL B/L CAROTID ARTERY - NORMAL

PROBLEMS: T2 Diabetes mellitus Multi nodular goitre LMN type lower cranial nerve involvement

(right 6th, left 7th bilateral 9,10,11) Gait ataxia Proximal weakness of lower limbs

Possible structures involved

Lower cranial nerves – LMN type (nuclear/infranuclear) (bilateral and asymmetric)

Cerebellum & its connections (mainly midline)

Muscle problem or a mixed UMN, LMN lesion.

Diagnosis with differentials:

Bilateral, symmetrical proximal > distal, flail weakness of lower limbs with intact reflexes, with gait ataxia, LMN type lower cranial nerve involvement without bladder or autonomic involvement of acute onset (over days).

Mitochondrial myopathies CNS demyelination – ADEM/multiple sclerosis Basal meningitis Botulism Tick paralysis Diphtheria Atypical viral encephalitis

symptom Mitochondrial myopathy

MS / ADEM Botulism Viral encephalitis

Tick paralysis

diphtheria

Weakness Hemiparesis/ recurrent prox flaccid quadriparesis

Pyramidal hemi/quadriparesis

Flaccid quadriparesis, descending

Focal, pyramidal

Flaccid quadriparesis, ascending

Flacid quadriparesis, descending

Cranial nerves

Only ocular Any cranial nerve

Pupils, any cranial nerve

Any cranial nerve

Ocular, bulbar

Any cranial nerve

Ataxia +/- +/- - -/+ - -

NCS Mild +/- +

Characteristic finding not present in our case

•Life span↓•Recurrence•Seizure •Psychosis •Cognitive dysfunction

•Recurrence•MRI lesions

•Pupillary paralysis•Respiratory paralysis

•Prodrome •ARAS, Respiratory center likely to be affected

•Presence of tick

•Neurological manifestation in proportion to pharyngeal

Normal

INVESTIGATIONS

CBC: Hb -12.2gm TC - 6200 DC – P-50% L-48% E-2% ESR – 5/12mm PCV – 34 MCV- 86 PLATELETS – 1.2 Lakhs

RFT:Blood Sugar - 169 mg

Blood Urea - 15mgs

Serum Creatinine - 0.7mgs

ELECTROLYTES:

Sodium- 134

Potassium – 4.2

Chloride – 97

Bicarbonate - 21

ECG : SR/NORTH WEST AXIS/S1S2S3 SYNDROME

X-ray chest P/A view – normal

7-6-11 FBS – 114mg

8-6-11 FBS – 129mg

USG NECK & THYRAID;

Isthmus 3cm RT lobe 3.2*1.3cm

2 nodes are normal 1*0.3cmAnother node 1.8*2 cm in RT Lobe

Nodules are heteroehoic Left lobe 4.1*2.1cm

3.3*1.8 cm heteroehoic lesion with multiple lesion seen in left lobe

Great vessels normal b/l submandibular gland & parotid gland normal No significant lymphadenopathy IMPRESSION; MULTINODULAR GOITER

HPE TO R/O malignancy

FNAC THYROID; NODULAR COLLAID GOITER WITH CYSTIC DEGENARATION,

NO E/O MALIGNANCY

Thyroid function test – normal CSF ANALYSIS

Protein – 48mg/dl Sugar – 112mg/dl Acellular

Urine myoglobin – negative Urine Bence Jones protein - negative Serum CPK – 126 IU, MB fragment -12 IU

Sr. calcium – 9.0 mg/dl Sr. phosphate – 3.6mg/dl Sr. magnesium – 1.8 mg/dl ANA – negative HIV – negative Mx – negative Sputum c/s – no growth Blood c/s – no growth

MRI report

Right optic nerve meningeoma Spine screening - normal

NEUROLOGY OPINION:

Clinically, RT lateral rectus palsy Left adductor nystagmus Left facial weakness Gag reflex diminished bilaterally Proximal > distal weakness DTR +++ Plantar – flexor MRI – normal study IMPREESSION: ? Demyelinating illness ?GBS variant ?miller fisher syndrome

ENT OPINION:

B/L tympanic membrane intact Nose mid line Throat normal B/L mild conductive hearing loss

OPHTHALMOLOGIST OPINION

RIGHT LEFT

EYE LIDS NORMAL NORMAL

EYE LASHES NORMAL NORMAL

CONJUCTIVA NORMAL NORMAL

CORNEA CLEAR , SENSATION INTACT CLEAR, SENSATION INTACT

IRIS COLOUR, PATTERN -NORMAL COLOUR, PATTERN -NORMAL

PUPIL PUPIL 3mm, REACTING TO LIGHT PUPIL 3mm, REACTING TO LIGHT

ANT CHAMBER NORMAL DEPTH NORMAL DEPTH

LENS MINIMAL CHANGES MINIMAL CHANGES

RETINOSCOPY +1.5/+1 +.5/+.5

EOM ABDUCTION RESTRICTEDDEXTRO ELEVATION, DEXTRO DEPRESSION RESTRICTEDLEVO ELEVATION, DEPRESSION NORMAL

EOM – FULL

•O/E alternating convergent squint +, Hirschberg test 15*

FUNDUS: B/L MEDIA CLEAR DISK & VESSELS NORMAL RT EYE – MACULA LT EYE – MACULA PIGMENT EPITHELIAL DETACHMENT+

COLOUR VISION BE – NORMAL FIELD OF VISION BE – NORMAL FORCED DUCTEL TEST RE NEGATIVE

IMPRESSION: MULTIPLE CRANIAL NERVE PALSY WITH LEFT EYE

NYSTAGMUS LEFT EYE MACULO DEGENERATIVE DISEASE

NCS

RIGHT PERONEAL NERVE RIGHT MEDIAN NERVE

Conduction velocity

34.08m/s >51

Prox CMAP Amplitude

1.0mV N>4.4

Conduction velocity

54.92m/s >48

Prox CMAP Amplitude

8.7mV N>4.4

NCS report

UL- median and ulnar CMAP latency amplitude and velocity F wave latency within limits

On proximal stimulation Segmental conduction block seen in Left median Nerve.

Median and ulnar SNAP’s within normal limits  LL- both peroneal and left tibial velocity reduced, Right peroneal amplitude reduced On proximal stimulation Segmental conduction blocks seen in

both tibial Nerves. Both peroneal and tibial F waves absent. Right sural SNAP latency prolonged, Left sural SNAP absent

Imp: suggestive of demyelinative radiculo neuropathy ( LL more affected than UL)

Course in the hospital

The reflexes diminished and became absent on the 4rd day of admission prompting the diagnosis of MFS following which plasma exchange was started

The facial weakness completely subsided in 1 week.

At the end of one week patient had only mild symmetric proximal weakness with ataxia, areflexia and right abducent palsy.

However the patient started developing paresthesias in both lower limbs in the 2nd week. But there was no objective sensory loss.

Facial weakness improves

Patient now able to look right

NEUROLOGIST REVIEW

CLINICALLY, CONCIOUS ,ORIENTED, PRESENTING WITH DIPLOPIA MRI BRAIN - NO VENTRICULO MEGALY,

NO SOL RT OPTIC MENINGIOMA

IMPRESSION : PT IMPROVING ATXIA , RT LR PALSY

CONTINUE PLASMA EXCHANGE

FINAL DIAGNOSIS

GBS – LOWER CRANIAL NERVE VARIANT BICKERSTAFF BRAINSTEM ENCEPHALITIS MILLER FISHER/BICKERSTAFF OVERLAP

Questions

Can unilateral abducent palsy be a feature of MFS / BBE?

Why was the patient diagnosed as BBE instead of MFS?

How do you explain the paresthesia? Why was nerve biopsy/ EMG not done?

CRITERIA FOR DIAGNOSING BBE Progressive external ophthalmoplegia

and ataxia of <4 weeks duration. Disturbance of consciousness OR

hyperreflexia Exclude other condition affecting the

brainstem and produce similar findings eg Brainstem stroke, tumor, lymphoma, ADEM,

Multiple sclerosis, botulism, pituitary apoplexy, neuro behcets, vasculitis.

Miller Fisher Syndrome

Epidemiology: Onset: Mean 40 years; Range 13 to 78 years Seasonal: Higher frequency in Spring (March

to May) Clinical prodrome: Respiratory most common Frequency: 25% of GBS in Japan; 1% of GBS

in US Associated infections

Campylobacter jejuni: Often serotype O-2 or O-10

Hemophilus influenzae: 7% of MFS patients with positive serology

Clinical Onset

Diplopia (Asymmetric) (80%) Myalgia & Paresthesias Vertigo & Ataxia

Eye External ophthalmoplegia (100%): Symmetric

or Asymmetric Pupillary dysfunction (42%): Mydriasis Ptosis (58%)

Ataxia (100%): Dysmetria; Gait ataxia; Arms & Legs

Areflexia (100%): By 1 week of disease Sensory

Distal & Facial paresthesias & dysesthesias (24%) Sensory loss: Minimal; Definite in 20%

Weakness: 20% Autonomic: Bladder disorders 16% Other Cranial nerve disorders

Oropharyngeal weakness (26%) Facial weakness (32%)

GBS – The cranial nerve variants MFS-Cranial nerve variants: Often associated

with IgG vs GQ1b or GT1b gangliosides GBS overlap: Ophthalmoplegia; Weakness; ± Ataxia Internal ophthalmoplegia: Dilated pupils; Light-near

dissociation Acute external ophthalmoplegia: Complete or partial Acute ataxia: May progress to Weakness & GBS Visual impairment Acute neuropathies with bulbar dysfunction:

Pharyngo-cervical-brachial variants Bickerstaff brainstem encephalitis: Brainstem signs

Laboratory CSF

Protein: 20 to 60 mg/dl Cells: Few or None; 0 to 5/mm3

Nerve conduction studies Sensory

Axonal loss SNAPs: Reduced amplitude

Motor Peripheral nerve: Normal CMAPs Facial: Reduced CMAP amplitude

F-waves: Prolonged; Dispersed; Absent H reflexes: Absent from soleus

Serum antibodies IgG vs GQ1b (80%) IgG staining of cerebellar molecular layer

MRI Cranial nerve enhancement (gadolinium) may

occur Brainstem or Cerebellar lesions: Some patients

Treatment: IV IG or plasmapheresis

Bickerstaff brainstem encephalitis Epidemiology: Most reports from Japan Antecedent illness (92%): Most commonly upper

respiratory infection Age: 3 to 91 years Onset: Diplopia or gait disorder most common Clinical: Brainstem signs

Reduced consciousness (74%): Drowsy, stupor or coma Ataxia: Often trunk & limb Eyes

Ophthalmoplegia, external (100%): Relatively symmetric Pupil disorders (34%) Ptosis (29%) Nystagmus (27%)

Other cranial nerves Facial diplegia (45%) Bulbar weakness (34%)

Weakness: Flaccid tetraparesis (60%); Respiratory failure

Pyramidal signs Tendon reflexes: Variable; Hyperreflexia to Absent Plantar responses (40%): Extensor

Sensory loss Small fiber (31%) Large fiber (16%) Hemisensory loss

Course Often good prognosis: Complete remission in 51%;

Death 4% Laboratory

Serum IgG binding to GQ1b ganglioside (66%) Electrophysiology

Motor axon degeneration

Clinical profile of patients with BBE

Antibody profile in BBE

Diagnostic Criteria for Guillain-Barrý Syndrome (Ashbury et al)

 Features required for diagnosis Progressive weakness of both legs and arms Areflexia

Clinical features supportive of diagnosis Progression over days to 4 wk Relative symmetry or signs Mild sensory symptoms or signs Cranial nerve involvement (bifacial palsies) Recovery beginning 2-4 wk after progression ceases Autonomic dysfunction Absence of fever at onset

Laboratory features supportive of diagnosis Elevated cerebrospinal fluid protein with < 10 cells/μL Electrodiagnostic features of nerve conduction slowing

or block

REFRENCES

Bickerstaff's brainstem encephalitis: clinical features of 62 cases and a subgroup associated with Guillain-Barre syndrome. (encephalitis) Brain. 2003 Oct;126(Pt 10):2279-90. Epub 2003

Jul 07 Odaka M, Yuki N, Yamada M, Koga M, Takemi T,

Hirata K, Kuwabara S.

Department of Neurology, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan.

A case of Guillain-Barré syndrome with bulbar palsy showing the elevations of the anti-GD1a and GT1b antibodies. Rinsho Shinkeigaku 2001 Apr-May;41(4-5):202-

5 [Article in Japanese] Ito S, Hirose Y, Mokuno K, Kusunoki S. Source Department of Neurology, Toyohashi Municipal

Hospital.

Unilateral Abducens Nerve Palsy as an Early Feature of Multiple Mononeuropathy Associated with Anti-GQ1b Antibody Ryuta Kinno,* Hiroo Ichikawa, Hiroto

Tanigawa, Kazuhiro Itaya, and Mitsuru Kawamura

Department of Neurology, Showa University School of Medicine, Tokyo, Japan

Follow up

At 45 days the patient came for follow up There was no demonstrable weakness Cranial nerves were normal Reflex were just elicitable Paresthesia however persisted Repeat nerve conduction planned 2 wks

later

Picture of the patient

Ophthalmoparesis

complete/partial

Symmetrical proximal weakness

Facial weakness

Ataxia