Peripheral Neuropathies 3 Flashcards
Idiopathic brachial plexitis (neuralgic amyotrophy): 1) clinical findings 2) diagnosis
1) Acute shoulder pain, followed within hours to days by numbness and weakness of the arm or hand. These symptoms rapidly plateau and are usually followed by gradual recovery over months.
Symptomatic diaphragm dysfunction due to unilateral or bilateral phrenic neuropathy (7 % of neuralgic amyotrophy)
2) primarily a clinical diagnosis supported by electrodiagnostic testing
Electrophysiologic studies:
Nerve conduction studies are supportive and can exclude more common mononeuropathies
EMG is important to document denervation
Nerve conduction abnormalities may not appear for up to several days after onset, and needle EMG may not become abnormal for 2–3 weeks.
MRI and magnetic resonance neurography of the brachial plexus and affected nerves may show abnormalities including focal thickening, increased T2 signal, and gadolinium enhancement.
Idiopathic brachial plexitis (neuralgic amyotrophy): 1) differential diagnosis 2) treatment 3) prognosis
1) Differential diagnosis:
- acute radiculopathy
- traumatic injury to the shoulder or plexus
- alternative causes of an acute plexopathy such as infection (eg, Lyme disease, HIV), diabetes, or malignancy
2) Most patients recover without treatment.
Physical therapy is helpful for aiding recovery and preventing complications.
Within days of onset, a tapering course of corticosteroids may be given
3) Most patients recover completely and recurrence is rare, although some patients may have permanent deficits
Mononeuropathy multiplex: 1) definition 2) clinical findings
1) Autoimmune attack on the vasculature of the peripheral nerves (the vasa nervorum) results in inflammation, occlusion, and ischemia in separate peripheral, cranial, and respiratory nerves throughout the body.
Mononeuropathy multiplex may be part of a systemic vasculitis or be isolated to the peripheral nerves (nonsystemic - very rare)
2) acute onset of motor weakness, which may be preceded by pain. A second nerve, often in a different extremity, may be affected.
In some instances, generalized vasculitic involvement of the peripheral nerves follows, which may include the nerves of the respiratory system, resulting in respiratory compromise.
In other cases, peripheral nerve involvement precedes a rapidly progressive generalized vasculitis.
Mononeuritis multiplex: associated medical conditions
- vasculitis
those that affect either small- or medium-sized arteries are the most commonly implicated.
Examples include the group of vasculitic disorders commonly associated with antineutrophil cytoplasmic autoantibodies (ANCA); ie, granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis, polyarteritis nodosa, and mixed cryoglobulinemia - rheumatoid arthritis and other collagen vascular diseases (eg, sarcoidosis)
- viral infections (eg, HIV, hepatitis B and C, cytomegalovirus)
- Lyme disease
- leprosy
- tumor infiltration
- lymphoid granulomatosis
- Diabetes mellitus (can cause multiple mononeuropathies but not typically as a rapidly progressive syndrome over days)
Mononeuropathy multiplex: 1) diagnosis 2) differential diagnosis 3) treatment
1)
- laboratory studies to support or exclude associated systemic vasculitic disorders
- nerve conduction studies and EMG
- nerve/muscle biopsy in selected patients
Systemic vasculitic neuropathy (when other organs are also involved)
Is usually diagnosed clinically based on the presence of neuropathy with clinical features that are typical for vasculitic neuropathy in the setting of an established or newly diagnosed primary or secondary systemic vasculitis
nonsystemic vasculitic neuropathy (when only the peripheral nervous system is involved - very rare)
Diagnosis largely depends on histopathologic evidence of vasculitis involving the peripheral nervous system and the exclusion of other known associated diseases.
Nerve biopsy is required for diagnosis.
Nerve conduction abnormalities may not appear for up to several days after the onset of the initial deficit, and needle EMG may not become abnormal for 2–3 weeks.
2)
- regional peripheral nerve syndromes (eg, brachial plexitis, diabetic amyotrophy),
- atypical polyneuropathy
- multiple compressive mononeuropathies
- Multifocal motor neuropathy
- hereditary neuropathy with liability to pressure palsies
3) In case of vasculitis, aggressive treatment with immunosuppressive agents, such as intravenous pulse cyclophosphamide, high-dose corticosteroids, or both may be needed.
Specific autoimmune diseases should be treated in consultation with a rheumatologist after the initial episode of mononeuropathy multiplex has been adequately controlled.
Difference between polyneuropathy and mononeuropathy multiplex
Polyneuropathies usually denote a diffuse process affecting all nerves more or less symmetrically, showing length-dependent signs and symptoms.
In mononeuropathy multiplex, the disease process affects one nerve at a time but eventually many of them, usually with considerable asymmetry.
Guillain Barre syndrome: 1) definition 2) pathogenesis
1) group of immune mediated disorders targeting the peripheral nerves
2) It is often triggered when an immune response to an antecedent infection or other event cross-reacts with shared epitopes on peripheral nerve (molecular mimicry).
All myelinated nerves (motor, sensory, cranial, sympathetic) can be affected.
Demyelination – In AIDP and the Miller Fisher syndrome variant form, a focal inflammatory response develops against myelin-producing Schwann cells or peripheral myelin. Demyelination is thought to start at the level of the nerve roots where the blood-nerve barrier is deficient. The breakdown of the blood-nerve barrier at the dural attachment allows transudation of plasma proteins into the cerebrospinal fluid.
Axonal degeneration occurs as a secondary bystander response;
Peripheral nerve remyelination occurs in recovery over several weeks to months. However, in a small percentage of patients, there is superimposed severe axonal degeneration with markedly delayed and incomplete recovery.
Axonal loss – Immune reactions against epitopes in the axonal membrane cause the acute axonal forms of GBS: AMAN and acute motor and sensory axonal neuropathy (AMSAN).
In the axonal variants of GBS, antibody and complement-mediated humoral immune response leads to direct axolemma injury. The primary immune process is directed at the nodes of Ranvier, leading to axonal involvement with conduction block caused by paranodal myelin detachment, node lengthening, sodium channel dysfunction, and altered ion and water homeostasis. This process can rapidly reverse in some cases but may progress to axonal degeneration in others. The motor nerves are involved at the ventral roots, peripheral nerve, and the preterminal intramuscular motor twigs. In the motor-sensory variant, sensory nerves also are affected.
Guillain Barre syndrome triggering factors
Up to two-thirds of patients give a history of an antecedent respiratory tract or gastrointestinal infection.
1) Infection
- Campylobacter jejuni infection – C. jejuni gastroenteritis is the most common precipitant of GBS, identified in approximately 25 percent of cases
C. jejuni can generate antibodies to specific gangliosides, including GM1, GD1a, GalNac-GD1a, and GD1b, which are strongly associated with AMAN and AMSAN.
C. jejuni infection can generate antibodies to the GQ1b ganglioside, a component of oculomotor nerve myelin. GQ1b antibodies are frequently found in variants characterized by ophthalmoplegia, such as MFS and Bickerstaff brainstem encephalitis. Antibodies to GT1a, which cross-react with GQ1b, have also been associated with bulbar forms of GBS
The rate of preceding C. jejuni infection varies by the form of GBS, being found in about 60 to 70 percent of acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN) cases and up to 30 percent of acute inflammatory demyelinating polyneuropathy (AIDP) cases
- Cytomegalovirus
Cytomegalovirus infections were associated with antibodies to the ganglioside GM2 and with severe motor and sensory deficits. - Influenza A and B
- HIV
- COVID-19 virus
- Zika virus
- Others – GBS has been reported following infection with the varicella-zoster virus, Epstein-Barr virus, herpes simplex virus, hepatitis E, chikungunya virus, Japanese encephalitis virus, and the bacteria H. influenzae, Escherichia coli, and M. pneumoniae
2) Other triggers — A small percentage of patients develop GBS after other triggering events such as:
- vaccines
- surgery
- trauma
- bone-marrow transplantation
- Hodgkin lymphoma
- systemic lupus erythematosus
- sarcoidosis
- medications (tumor necrosis factor-alpha antagonist therapy, tacrolimus and suramin, Isotretinoin, Immune checkpoint inhibitors)
Guillain Barre syndrome subtypes and clinical findings
Acute inflammatory demyelinating polyneuropathy - AIDP
Acute motor axonal neuropathy – AMAN
Acute motor and sensory axonal neuropathy – AMSAN
GQ1b syndromes:
1) Miller Fisher syndrome
2) Bickerstaff brainstem encephalitis
3) Pharyngeal-cervical-brachial weakness
Rare variants:
1) Paraparesis
2) Acute pandysautonomia
3) Pure sensory GBS
4) Facial diplegia and distal limb paresthesia
5) Acute bulbar palsy
AIDP clinical findings
Progressive and symmetric muscle weakness and absent or depressed deep tendon reflexes.
Patients may also have sensory symptoms and dysautonomia.
Examination findings:
A) Weakness — The weakness in GBS can vary from mild difficulty with walking to near complete paralysis of all limb, facial, respiratory, and bulbar muscles, depending on disease severity and clinical subtype.
Limb weakness – Classically, there is flaccid proximal and distal arm and leg weakness. The weakness is usually symmetric and starts in the legs, but begins in the arms or facial muscles in about 10 percent of patients. Most patients progress to weakness in both arms and legs by the nadir.
Cranial nerve and bulbar symptoms – Facial nerve palsies occur in more than 50 percent with AIDP, and oropharyngeal weakness eventually occurs in 50 percent. Oculomotor weakness occurs in about 15 percent of patients.
Cranial nerve symptoms including ophthalmoplegia are also diagnostic features of some variant forms of GBS.
Severe respiratory muscle weakness necessitating ventilatory support develops in 10 to 30 percent with GBS
B) Deep tendon reflexes — Decreased or absent deep tendon reflexes in the arms or legs are found in approximately 90 percent of patients at presentation. Most patients will develop hyporeflexia as symptoms progress to the nadir.
However, normal or even increased deep tendon reflexes may be found in some patients with GBS. These include patients with the acute axonal neuropathies and Bickerstaff brainstem variant forms.
C) Sensory involvement – Paresthesias in the hands and feet are reported by more than 80 percent of patients, but sensory abnormalities on examination are frequently mild.
Pain due to nerve root inflammation, typically located in the back and extremities, can also be a presenting feature and is reported during the acute phase by two-thirds of patients with all forms of GBS
D) Dysautonomia – The prevalence of autonomic dysfunction ranges from 38 to 70 percent of patients with GBS
The most frequent autonomic symptoms are:
Ileus (42 percent)
Hypertension (39 percent)
Hypotension (37 percent)
Fever (29 percent)
Tachycardia or bradycardia (27 percent)
Urinary retention (24 percent)
The syndrome of inappropriate antidiuretic hormone secretion (SIADH), which may be due to autonomic involvement, is an infrequent complication of GBS
Uncommon features – Unusual features of GBS include papilledema with severely elevated CSF protein, facial myokymia, hearing loss, meningeal signs, vocal cord paralysis, and mental status changes
In addition, posterior reversible encephalopathy syndrome has been associated with GBS in adults and children, likely related to acute hypertension from dysautonomia
GBS duration of symptoms
GBS symptoms typically progress over a period of two weeks.
By four weeks after onset, more than 90 percent of patients have reached the nadir of the disease.
Progression over four to eight weeks is sometimes called subacute inflammatory demyelinating polyradiculoneuropathy (SIDP).
Disease progression for more than eight weeks is consistent with the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
Acute motor axonal neuropathy
Most cases are preceded by C. jejuni infection and occur in Asia, particularly in young people. AMAN is more frequent in the summer. The pathology predominantly involves axon loss.
Deep tendon reflexes may be preserved in some patients with AMAN
This form of GBS is distinguished from AIDP by its selective involvement of motor nerves.
Sensory nerves are not affected.
It may progress more rapidly, but the presenting clinical features of AMAN are otherwise similar to those of AIDP.
Evidence of early axonal involvement on electrodiagnostic studies is seen as a reduction of CMAP amplitudes on nerve conduction studies
AMAN associated antibodies
The development of AMAN has been associated with IgG antibodies to the gangliosides GM1, GD1a, GalNac-GD1a, and GD1b, which are present in peripheral nerve axons.
These antiganglioside antibodies can be induced by C. jejuni infection owing to molecular mimicry.
The pathophysiology is due to antibody and complement-mediated nerve axon damage of varying severity.
Acute motor and sensory axonal neuropathy
A more severe form of AMAN, in which both sensory and motor fibers are affected with marked axonal degeneration, frequently causing delayed and incomplete recovery.
Clinically, AMSAN resembles the AMAN variant but with additional sensory symptoms.
Electrodiagnostic studies on patients with AMSAN show severely reduced or absent CMAP and SNAP amplitudes.
Axon degeneration in these patients is demonstrated by extensive active denervation needle electrode EMG studies.
AMSAN is also associated with antiganglioside antibodies to GM1, GD1a, GalNac-GD1a, and GD1b
Miller Fisher syndrome
5 to 10 percent of cases in the United States and Europe
Ophthalmoplegia, ataxia, and areflexia
one-quarter of patients who present with MFS will develop some limb weakness.
Incomplete forms include acute ophthalmoplegia without ataxia and acute ataxic neuropathy without ophthalmoplegia. Some patients with MFS develop fixed, dilated pupils
Antibodies against GQ1b are present in 85 to 90 percent of patients with MFS
Electrodiagnostic studies in patients with MFS may reveal reduced or absent sensory responses without slowing of sensory conduction velocities.
Those with clinical weakness may show abnormalities on nerve conduction studies typical of AIDP, such as increased distal latencies or conduction block with temporal dispersion of motor responses.
Bickerstaff brainstem encephalitis
Encephalopathy with ophthalmoplegia and ataxia
facial weakness
bulbar symptoms
pupillary abnormalities
mild limb weakness
reflexes may be normal or brisk
It is associated with anti-GQ1b antibodies and can respond to intravenous IVIG or plasma exchange
Pharyngeal-cervical-brachial weakness
Acute weakness of the oropharyngeal, neck, and shoulder muscles with swallowing dysfunction
This form may overlap with MFS or BBE
Patients with the PCB variant may also have facial weakness but may be distinguished from those with AIDP because leg strength and leg reflexes are usually, but not always, preserved
Detailed serial nerve conduction studies indicate a localized pattern of neuronal damage similar to AMAN
In a study of 100 PCB patients, half carried IgG anti-GT1a antibodies (associated with bulbar dysfunction), which often cross-react with GQ1b, and a quarter displayed IgG antibodies against GM1 or GD1a, which are often seen in AMAN
Guillain Barre syndrome diagnostic criteria
CSF in Guillain barre syndrome
The typical finding with lumbar puncture in patients with GBS is an elevated CSF protein with a normal white blood cell count
The elevated protein may be due to increased permeability of the blood-nerve barrier at the level of the proximal nerve roots.
CSF protein elevations varied in one study from 45 to 200 mg/dL
The albuminocytologic dissociation varies by time since symptom onset.
It may be present in 50 to 66 percent of patients in the first week after the onset of symptoms and ≥75 percent of patients in the third week
The CSF cell count is typically normal (ie, <5 cells/mm3) but may be elevated up to 50 cells/mm3
Electrodiagnostic studies in Guillain Barre syndrome
Electrodiagnostic testing may not be needed for the diagnosis of GBS in patients with typical symptoms who are found to have an albuminocytologic dissociation on CSF analysis.
Findings may be normal early in the disease course.
If electrodiagnostic testing performed at initial presentation is nondiagnostic, repeat testing may be performed one to two weeks after the first study. Abnormal findings are typically most pronounced approximately three to four weeks after the onset of weakness.
Progression of abnormal findings that support the diagnosis of the common demyelinating forms of GBS include:
-Prolonged or absent F waves and absent H reflexes as the earliest findings
-Increased distal latencies and conduction blocks with temporal dispersion of motor responses
-Significant slowing or absent response on nerve conduction velocities not seen until the third or fourth week
-Needle EMG of weak muscles showing reduced recruitment or denervation
Sural sparing, when noted, also reinforces the suspicion for GBS since this finding is usually not observed in length dependent neuropathies
Ancillary studies, such as facial NCS and blink reflex testing, may be used to show abnormal conduction in patients with GBS and bulbar symptoms.
Electrodiagnostic studies may also be useful to identify the main variants of GBS by identifying demyelinating (eg, acute inflammatory demyelinating polyneuropathy) or axonal (eg, AMAN) pathophysiology
●Demyelinating forms of GBS are supported by features of demyelination, including increased F wave latency, prolonged distal motor latency, conduction blocks, temporal dispersion, and decreased motor nerve conduction velocity.
●Axonal forms of GBS are supported by decreased distal motor and/or sensory amplitudes. In contrast with demyelinating forms, there is typically no sensory nerve involvement and F waves may be absent but are not significantly prolonged. In addition, there is no significant slowing of conduction velocities, increase in distal latencies, or temporal dispersion.
Autoantibody testing in Guillain Barre syndrome
The serum of patients with acute axonal neuropathies such as AMAN and acute motor and sensory axonal neuropathy (AMSAN) have frequently been found to have anti-GM1 IgG and anti-GD1a antibodies
Anti-GalNac-GD1a and anti-GD1b have also been associated with axonal forms of GBS
(Anti-GM2 IgM antibodies have been noted in 30 to 50 percent of patients with cytomegalovirus (CMV)-associated GBS, but anti-GM2 antibodies also occur in patients with CMV who do not have GBS)
Serum IgG antibodies to GQ1b are useful for the diagnosis of MFS, having a sensitivity of 85 to 90 percent. GQ1b is a component of oculomotor nerve myelin and may also be present in patients with Bickerstaff brainstem encephalitis, the pharyngeal-cervical brachial variant, and other patients with GBS with ophthalmoplegia
Anti-GT1a antibodies that cross-react with GQ1b have been reported in patients with the PCB variant
Some patients with PCB form of GBS may have antibodies against GM1 or GD1a, which are more frequently seen in patients with AMAN who also present with prominent motor weakness
MRI in Guillain Barre syndrome
MRI may reveal thickening and enhancement of the intrathecal spinal nerve roots and cauda equina
The anterior spinal nerve roots may be selectively involved, but, in other cases, both the anterior and posterior spinal nerve roots are involved
Guillain Barre syndrome differential diagnosis (cerebrall, cerebellar, spinal)
Guillain Barre syndrome differential diagnosis (peripheral, neuromuscular, muscle)
Guillain Barre syndrome treatment
PLEX is usually given in four to six treatments over 8 to 10 days
Electrodiagnostic criteria of CIDP
CIDP diagnostic criteria
Multifocal motor neuropathy diagnostic criteria
The diagnosis is supported by nerve conduction studies that demonstrate focal demyelination and conduction block in motor nerves and normal sensory nerves
However, some patients have a similar clinical disorder but lack conduction block on nerve conduction studies, and this has been termed multifocal motor neuropathy without conduction block (MMNWOCB)
Paraneoplastic neuropathy syndromes
