gb syndrome(miller-fisher variant)

Guillain-Barre Syndrome : 

Guillain-Barre Syndrome (Miller-Fisher variant) Ptd By Lt Col K Mohan

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Introduction

Landry Guillain Barré Syndrome : 

Landry Guillain Barré Syndrome Descriptions of progressive numbness and weakness over a short period followed by spontaneous recovery exist in medical papers of the early 19th century. Certainly the best description of 'ascending paralysis' in this period was made by a Frenchman named Jean Baptiste Landry in 1859.

Guillain Barré Syndrome : 

Guillain Barré Syndrome In 1916 the French army neurologists Guillain and Barré's observation that this weakness occurred with albumino-cytologic dissociation (an elevated CSF protein with a normal CSF cell count) allowed this entity to be distinguished from polio and other neuropathies.

Types/Variants of GBS : 

Types/Variants of GBS Acute Inflammatory Demylinating Polyradiculoneuropathy (AIDP) Acute Motor-Sensory Axonal Neuropathy (AMSAN) Acute Motor Axonal Neuropathy (AMAN) Miller Fisher Variant Pharyngeal-Cervical-Brachial Variant Acute Pandysautonomia

Epidemiology : 

Epidemiology Most common cause of acute flaccid paralysis in Western countries Overall incidence 1-2/100,000 All age groups can be affected, however more common in elderly Bimodal peak, small peak in young adults and larger peak in elderly Male: Female = 1.25: 1

Epidemiology - MFS : 

Epidemiology - MFS Frequency : 1% of GBS in US. 25% of GBS in Japan 5% of all cases Age : Mean 40 years Range 13 to 78 years First reported in 1932- Charles Miller Fisher

Etiopathogenesis : 

Auto immune response triggered by Infections Campylobacter Mycoplasma EBV, CMV, HSV, Recently acquired HIV infection Vaccinations Surgery,trauma Systemic processes, such as Hodgkin's disease SLE Sarcoidosis Etiopathogenesis

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Pathophysiology

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Pathophysiology

Pathophysiology : 

Exposure to infectious agents/vaccines triggers an autoimmune response mistargeted to host nerve tissues -A form of antigenic mimicry The targets of such immune reactions are ganglioside present in high concentrations in peripheral nerve myelin GBS- GM1,GD1 gangliosides (present in spinal nerves) MFS- GQ1b gangliosides (present in cranial nerves) Pathophysiology

Pathophysiology : 

End result – Inflammation of myelin Conduction block Muscle paralysis Sensory loss/Autonomic disturbance Main lesion - Acute inflammatory demyelinating neuropathy In patients with Campylobacter-associated disease, acute axonal degeneration Pathophysiology

Clinical Manifestations : 

Clinical Manifestations Preceeding H/O Resp tract /GI infection Weakness and unsteadiness . The weakness typically starts in the lower extremities, usually symmetric and ascends into the upper extremities. This progression may extend from hours to days and the patient usually presents few days to a week after onset of symptoms Weakness varies from mild difficulty in walking to complete paralysis of all extremities Quadriplegia in 30%. Severe respiratory muscle weakness (30%)

Clinical Manifestations : 

Clinical Manifestations Pain and paraesthesias Pain may be the initial manifestation – deep aching pains in the weakened muscles Tingling & numbness(80%) Cranial nerve involvement (35-50%) Mostly seventh CN Lower cranial nerves- Bulbar weakness (Dysphagia, drooling ) Tongue involvement is common (50%) and usually symmetric. Respiratory failure Usually secondary to muscle weakness but occasionally related to aspiration

Physical Examination : 

Physical Examination Symmetric limb weakness Areflexia common early in most (70%) but not all patients. Minimal loss of sensation despite paresthesias Usually loss of proprioception Pain and temp preserved. Clinical Manifestations

Physical Examination : 

Physical Examination Signs of autonomic dysfunction(40-50%) Cardiac dysarrhythmias (asystole, bradycardia, sinus tachycardia, and atrial/ventricular tachyarrhythmias) Orthostatic hypotension Transient or persistent hypertension Paralytic ileus Bladder dysfunction Abnormal sweating Clinical Manifestations

Miller Fisher Syndrome : 

Miller Fisher Syndrome Onset usually with diplopia (80%), myalgia & paraesthesias and vertigo & Ataxia External ophthalmoplegia (100%) - Mostly Symmetric Pupillary dysfunction (42%) - Mydriasis Ataxia (100%) - Gait ataxia, Dysmetria; Arms & Legs (The ataxia tends to be out of proportion to the degree of sensory loss) Areflexia (100%) - By 1 week of disease Clinical Triad : Ophthalmoplegia, Ataxia, Areflexia

Miller Fisher Syndrome : 

Miller Fisher Syndrome Distal & Facial paresthesias & dysesthesias (24%) Sensory loss: Minimal (Definite in 20%) Limb Weakness: 20% Autonomic : Bladder disorders 16% Oropharyngeal weakness (26%) Facial weakness (32%)

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Usually progresses over a period of 2 weeks 66% reach nadir in 2 weeks, 92% in 3 weeks; by definition must peak at 4 weeks Brief plateau phase then improvement and gradual resolution over weeks to months (usually 7 months) Progression for more than 8 weeks - CIDP Clinical progression

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Initial diagnosis - Clinical Cerebrospinal fluid (CSF) analysis typically reveals Normal pressure Normal cell count (Less than 5 cells/cmm ) Elevated protein conc. (Greater than 50 mg/dL) The spinal fluid findings may be normal within the first 48 hours of symptoms, and occasionally, the protein may not rise for a week. If CSF pleocytosis is noted, other diseases associated with GB syndrome eg, HIV infection, Lyme disease, malignancy, and sarcoidosis should be considered Diagnosis

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Neurophysiologic studies are the most specific and sensitive tests for diagnosis of the disease Nerve conduction studies(NCS) and needle electromyography(EMG) demonstrate a variety of abnormalities indicating evolving multifocal demyelination Slowed nerve conduction velocities Partial motor conduction block Abnormal temporal dispersion Prolonged distal latencies Absent F waves Diagnosis

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Nerve conduction studies(NCS)

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Antibodies: Not routinely carried out in classical GBS IgG antibodies to GQ1b is useful for diagnosis of MFS(sensitivity-90%) Diagnosis

Imaging : 

Imaging MRI is sensitive but not specific Spinal nerve root enhancement with gadolinium is a nonspecific feature seen in inflammatory conditions and is caused by disruption of the blood-nerve barrier Selective anterior nerve root enhancement appears to be strongly suggestive of GBS The cauda equine nerve roots are enhanced in 83% of patients Diagnosis

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National Institute of Neurological Disorders and Stroke (NINDS) Criteria Required features include : Progressive weakness of more than one limb, ranging from minimal weakness of the legs to total paralysis of all four limbs, the trunk, bulbar and facial muscles, External ophthalmoplegia Areflexia. While universal areflexia is typical, distal areflexia with hyporeflexia at the knees and biceps will suffice if other features are consistent. Diagnostic criteria

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Supportive features include : Progression of symptoms over days to four weeks Relative symmetry Mild sensory symptoms or signs Cranial nerve involvement, especially bilateral facial nerve weakness Recovery starting two to four weeks after progression halts Autonomic dysfunction No fever at the onset Elevated protein in CSF with a cell count <10 mm3 Electrodiagnostic abnormalities consistent with GBS Diagnostic criteria

Differential Diagnosis : 

Differential Diagnosis Botulism Brain stem encephalitis Myasthenia Gravis Lyme disease Myelopathies Acute neuropathies Tic paralysis

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Differential Diagnosis

Muscle (acute myopathies) : 

Muscle (acute myopathies) Inflammatory myopathy (polymyositis,dermatomyositis) Rhabdomyolysis Acute alcoholic necrotizing myopathy Periodic paralyses (hypo,hyperkalemia) Metabolic (hypophosphatemia,hypomag) Constitutional symptoms, Proximal weakness and normal reflxes

Neuromuscular Junction : 

Neuromuscular Junction Myasthenia Gravis Fatigue Normal reflexes ANS spared Botulism Sensory system spared Normal reflexes Tick paralysis Deeply resemble GBS Normal CSF

Nerve (acute neuropathies) : 

Nerve (acute neuropathies) Diptheria Porphyria Lyme disease Drugs & Toxins (arsenic, thallium, lead) Vasculitis (lupus, polyarteritis) Paraneoplastic and Paraproteinemias Multifocal motor neuropathy CSF/EMG/NCS

Anterior Horn Cell (Motor neuron disease) : 

Anterior Horn Cell (Motor neuron disease) Poliomyelitis Acute flaccid paralysis- proximal weakness Sensory system intact CSF pleocytosis Other inherited spinomuscular atrophies Anterior spinal artery syndrome

Spinal Cord(corticospinal tract diseases) : 

Spinal Cord(corticospinal tract diseases) Inflammatory (transverse myelitis) Subacute combined degenerative (B12 deficiency) Spinal Cord infarction Other myelopathies (spondylosis, epidural abscess or hematoma) Early bowel and bladder dysfunction & sensory level

Brain : 

Brain Brain stem stroke Multifocal lesions (multiple metastases, disseminated encephalomyelitis, mlutiple infarcts or hemorrhages) Altered sensorium, ANS spared, Hyper reflexia

Differential Diagnosis - MFS : 

Differential Diagnosis - MFS Brain stem stroke Brain stem encephalitis Wernicke’s encephalopathy Polyneuropathies Myasthenia gravis and other NeuroMuscular junction disorders

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The main modalities of therapy for Guillain-Barré syndrome and Miller- Fisher syndrome include Administration of intravenous immune globulin Plasmapheresis Definitive therapy is recommended for patients who Progress beyond four weeks Are unable to walk unaided Demonstrate worsening vital capacities Require mechanical ventilation Have significant bulbar weakness Management

Management : 

Management Intravenous immune globulin(IVIG) IVIG acts by neutralizing neuromuscular blocking antibodies. Most helpful in reducing the severity of the disease, as well as the duration of symptoms. IVIG regimens Daily intravenous immunoglobulin for 5 days at a dose of 0.4 gm/kg per day 2 gm/kg of intravenous immunoglobulin given as a single dose or 1gm/kg for 2 days.

IVIG : 

IVIG May increase serum viscosity and tromboembolic events May increase frequency of migraines May cause aseptic meningitis Six-fold increase in ESR lasting two to three weeks Apparent hyponatremia

Management : 

Management Plasmapheresis May decrease the severity and shorten the duration of illness. Most beneficial when started within 7 days of the onset of symptoms but is still beneficial in patients treated up to 30 days after disease onset.

Management : 

Management Results of plasmapharesis and intravenous immunoglobulin seem similar, with possibly fewer side effects seen with intravenous immunoglobulin. Combining plasma exchange and IVIG neither improved outcomes nor shortened the duration of illness Although steroids have been previously used to treat Guillain-Barré syndrome, current data suggest that there is no benefit for these agents.

Supportive Therapy : 

Supportive Therapy Cardio-pulmonary monitoring Vital signs and respiratory capacity Heart Rate BP Resp Rate Chest expansion Single breath count Breath holding time SPO2. Indication for ventillatory support PaO2 < 80 mm/Hg, vital capacity < 15 ml/kg of body weight significant fatigue

Prognosis : 

Prognosis In general most patients show a full recovery. 85% of patients will achieve a full and functional recovery within 6-12 months and the remainder will be able to walk unaided. 7-15% of patients will have permanent neurological sequelae including bilateral foot drop, intrinsic hand muscle wasting, sensory ataxia, dysesthesia (mostly in cases involving axonal damage) Despite intensive care, 3-4% of patients die Relapse rate 5-10%(Usually in children)

Conclusion : 

Conclusion Gullain Barre syndrome an autoimmune disorder triggered by some infections/vaccines resulting in an acute infalammatory progressive polyneuropathy. GBS is a heterogenous syndrome with several variant forms Miller-Fisher syndrome is a variant of Gullain Barre syndrome Clinical triad : ophthalmoplegia,ataxia and areflexia Diagnosed by Clinical presentation,electrophysiological studies and CSF analysis. Managed by IVIG/plasmapheresis with good prognosis

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