Peripheral Neuropathy: Part II Flashcards
(104 cards)
1
Q
An acute inflammatory polyradiculoneuropathy with resultant weakness with a possibility of paralysis and diminished reflexes
A
Guillain-Barré Syndrome (GBS)
2
Q
pathophys of Guillain-Barré Syndrome (GBS)
A
- a post-infectious, immune-mediated process
- infectious agents induce production of antibodies that breakdown myelin/damage axon in PNS
3
Q
causes of GBS
A
- MC infectious illness (respiratory/GI) in wks prior to onset
- Campylobacter jejuni - MC identified etiology
- Cytomegalovirus (CMV) - 2nd MC
- Other: EBV, M. pneumoniae, VZV, HIV
- Vaccinations - GBS has been associated w/ Menactra, Covid vaccine, Shingrix
4
Q
GBS is MC in who/when?
A
- Male-to-female ratio of 1.5:1
- Age risk is bimodal
- young adulthood (ages 15-35 y)
- middle-aged and elderly persons (ages 50-75 y)
5
Q
MC GBS variant
A
Acute inflammatory demyelinating polyneuropathy (AIDP)
6
Q
presentation of GBS
A
- Onset - 1-4 wks after a (benign) rsp or GI illness
- Presentation - 1 wk after onset of sx
- Initial sx
- Paresthesias - finger/toes moving proximally - sensory before motor sx
- Pain - throbbing/aching even w/ minimal movements - shoulder, back, buttocks, and thighs
- Proximal muscle weakness of LE “rubbery legs”
— 10% will have it begin in arms/face
— weakness progresses over hrs-days ascending symmetrically to involve entire body - later sx
- Muscle weakness → paralysis
— Legs →arms→truncal muscles→rsp→CN
— Rsp muscles: DOE, SOB, poor inspiratory effort, diminished breath sounds
— CN involvement: Facial droop, diplopia, ptosis, impaired EOM, ophthalmoplegia, pupillary dysfunction, dysarthria, dysphagia
- ANS dysfunction (Dysautonomia) - in 70% of pts
— tachycardia (MC), bradycardia, other arrhythmias, fluctuating BP, orthostatic hypotension, urinary retention, ileus, and anhidrosis - PE
- Diminished/absent DTRs early in course
- Muscle weakness→paralysis
- Impaired proprioception otherwise objective sensory findings are minimal
7
Q
work up for GBS
A
- serum labs WNL; used to r/o DDX
-
LP = albuminocytologic dissociation
- elevated CSF protein w/ normal WBC
- (+) within 1 wk of sx onset (MC) -
Electrodiagnostic Studies
- Confirms polyneuropathy
- Differentiates demyelinating vs axonal variants of GBS
- Results most pronounced 2 wks after onset of weakness
- nml study (early in course) does NOT r/o GBS = do serial studies -
MRI brain/spine w/ gadolinium - sensitive but not specific for GBS
- spine - thickening & enhancement of intrathecal spinal nerve roots and cauda equina
- brain - enhancement of CN roots
8
Q
management for GBS
A
-
Admit until plateau period has been reached
- avg time to plateau - 12-28 d
- ⅓ of pts require ICU d/t rsp failure - Consults to consider
- Neuro - will assist in dx & tx
- pulm - rsp management & vent support - Serial bedside PFT - q4h assessing pulm muscle strength
- cardio - cardiac arrhythmias or labile BP
- Surgery - if need for trach or enteral feeding tubes - ANS support
- Cardiac monitor, frequent BPs, fluids
- BP
— HTN - esmolol or nitroprusside
— Hypotension - IV fluids & supine
- HR
— Tachycardia - rarely severe enough for tx
— Bradycardia - atropine or external pacemaker (severe)
- Frequent assessment of BS (for ileus)
- I&O’s - assessing urinary retention - Immunotherapy - Plasmapheresis vs IVIG w/n 4 wks of sx onset
- Pain control
- 1st: NSAIDs, anticonvulsants (gabapentin/carbamazepine) or TCA (amitriptyline)
- careful w/ opiates if have dysautonomia - monitor for ileus
- epidural morphine for severe refractory pain -
Motor dysfunction
- PT & OT early on; inpatient rehab if persistent
- Speech therapy for significant oropharyngeal weakness (dysphagia, dysarthria) - DVT prophylaxis if unable to ambulate frequently - Lovenox, compression stockings and/or intermittent pneumatic compression
9
Q
indications for immunotherapy for GBS
A
non-ambulatory pts and ambulatory pts not recovering w/n 4 wks of sx onset
10
Q
which immunotherapy removes autoantibodies, immune complexes, cytotoxic constituents
more time consuming requiring 4-6 treatments over 8-10 days
GBS
A
Plasmapheresis
11
Q
which immunotherapy is derived from donated plasma; supplements the pts immune response
requires less time - one tx daily x 5 d
GBS
A
IVIG
12
Q
clinical course of GBS
A
- Average nadir is 12 d - can take up to 4 wk
- Followed by a plateau of unchanging sx
- recovery begins 2-4 wks after progression stops - Then gradual improvement of sx
- mean time to recovery is 200 d
13
Q
poor prognosis factors of GBS
A
- Older age
- Rapid onset (<7 d) prior to presentation
- Severe muscle weakness on admission
- Need for vent support
- avg distal motor response amplitude reduction to 20% of nml (2-4 wks after onset) on NCS
- Preceding diarrheal illness
14
Q
2-5% of GBS patients will develop ____ resulting in a chronic relapsing weakness
A
chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
15
Q
long-term monitoring for GBS
A
- Pt ed on realistic recovery goals and possible relapse
- 80% pts walk independently at 6 mo
- 60% attain full recovery w/n 12 mo - Monitor for depression and anxiety related to initial loss of quality of life
16
Q
relapse of GBS occurs in ?% of pts, closing monitoring and pt education to recognize sx are important
A
10%
17
Q
Motor nerve action potential releases ____ into the synaptic cleft (temporary depletion of presynaptic ____ - known as presynaptic rundown)
A
ACh
18
Q
ACh attaches to the ACh receptor (AChR) on the postsynaptic fold of the muscle cell resulting in ?
A
muscle contraction
19
Q
Acetylcholinesterase breaks down Ach to prevent ?
A
prolonged muscle contraction
20
Q
An autoimmune disorder presenting with progressively reduced muscle strength with repeated use and recovery of muscle strength after a period of rest
A
Myasthenia Gravis (MG)
21
Q
pathophys of Myasthenia Gravis (MG)
A
- antibodies against ACh nicotinic postsynaptic receptors (AChR) at neuromuscular junction (NMJ) of skeletal muscles = AChR destruction & loss of postsynaptic folds
- No receptors = over release of ACh from pre-synapsis to create adequate motor response
- repeated use of NMJ + presynaptic rundown = MG sx
22
Q
cause of MG
Myasthenia Gravis
A
Idiopathic
-
2 types of autoantibodies
- anti-AChR antibody (MC)
- anti-MuSK (muscle-specific tyrosine kinase) antibodies - Few pts will test negative for sero-antibody and still have clinical dx of MG
- Thymic disease is found in majority with AChR antibodies - thymoma, thymic hyperplasia
- Drugs - many shown to induce or exacerbate MG
23
Q
MG is MC in who/when?
A
uncommon
- Females - 20-30 y
- Male - 50-70 y
- Infantile - transient neonatal MG occurs in infants of myasthenic mothers who acquire anti-AChR antibodies via placental transfer of IgG
24
Q
presentation of MG
A
-
Fluctuating msk weakness and true muscle fatigue
- worsens w/ use and improves with rest
- worse later in day/evening or after exercise - Ocular (initial sx in > 50%) (CN III, IV, VI)
- binocular diplopia & weak EOM testing
— diplopia disappears when the patient closes one eye
— EOM testing reveals a general weakness to all ocular muscles
— Pupils are not affected in MG - Ptosis - unilateral (can be alternating) or bilateral
- Weakness confined to eyes in 15% of pts
- Bulbar muscle weakness (CN IX-XII)
- weakness w/ prolonged chewing
- dysphagia: nasal regurg, difficulty in handling secretions, choking on liquids
- dysarthria: slurring of speech
- dysphonia: nasal sound to voice or soft voice - Facial (CN VII)
- flat affect
- unable to smile or completely close eyes - Neck muscle weakness
- aching and fatigue often in the extensors first = “dropped head syndrome” later in day - Limb
- proximal muscle weakness w/ UE > LE with repetitive use - Nml DTR, sensation and coordination
- Rsp muscles - “myasthenic crisis”
- spontaneously or precipitated by event or meds
25
this presention of MG is the **weakness of diaphragm and intercostal muscles** lead to hypoventilation and rsp collapse requiring ventilation assistance
the muscle weakness will mask normal signs of rsp distress, such as accessory muscle use
myasthenic crisis
26
what is the "warning" sign of myasthenic crisis?
increasing generalized muscle weakness & bulbar muscle weakness
27
what events/meds can precipate myasthenic crisis?
infection, surgical procedure, pregnancy, childbirth, tapering of immunosuppressive medications
28
clinical course of MG
1. sx may resolve spontaneously for wks or longer
2. Relapses may result in new sx with a progression of recurrent sx becoming more persistent
3. sx progression usually peaks within first 3 yrs of dz onset
- eyes/face → neck→ upper limbs→ hands → lower limbs
29
DDX of MG
1. Lambert Eaton Myasthenic Syndrome (LEMS)
1. Botulism
1. Thyroid disease
1. Intracranial mass lesion (ocular symptoms only)
1. Chronic Progressive External Ophthalmoplegia (ocular symptoms only)
1. Medication induced myasthenia
1. Congenital myasthenic syndrome
30
work-up for MG
1. ice pack test - **(+)MG if improvement of ptosis**
2. Serology
- _ACh receptor ab_
--- present in 85% of pts w/ generalized disease
--- performed _**BEFORE** immune modulating therapy_ to avoid false (-) ab results
- _MuSK ab (muscle specific receptor tyrosine kinase)_
--- 35-50 % of pts w/ generalized MG (-) AChR-Ab
--- **(+) MuSK ab = < likely thymic-related dz**
- _Seronegative MG_
--- 6-12% (-) for both ab
- more likely to have **purely ocular disease**
3. Additional Serology
- _anti–striated muscle (anti-SM) Ab_
--- can be positive with (+) anti-AChR/anti-MuSK ab
--- (+) 30% of pts w/ MG
--- (+) 80% of pts w/ **thymoma**
4. Imaging
- _CT chest w/o contrast_ to assess for *thymoma*
5. Electrodiagnostic
- **Repetitive Nerve Stimulation (RNS) (MC)** - **smaller excitatory postsynaptic potentials (EPSPs)** d/t repetitive stimulation of the NMJ depleting Ach
- **Single-fiber electromyography (SFEMG)** _(most sensitive)_ - _increased interval between 1st & 2nd AP_ - **NOT SPECIFIC FOR MG**
31
a modified motor NCS that repetitively stimulates the NMJ of a specific muscle
most frequently used electrodiagnostic test for MG
Repetitive Nerve Stimulation (RNS)
32
normal response of Repetitive Nerve Stimulation (RNS)
all (EPSPs) exceed their threshold to generate an action potential
33
less readily available but the most sensitive diagnostic test for MG
records the action potentials of two muscle fibers innervated by the same motor axon
Single-fiber electromyography (SFEMG)
34
CI of Single-fiber electromyography (SFEMG)
had botox within last 12 mo
35
tx for MG
1. _symptomatic therapy_ - **AChI (1st line)** - **pyridostigmine**
2. chronic immunomodulators - glucocorticoids, immunosuppressives
- **Prednisone** - reduce the production of antibodies
--- _High dose steroids_ *only* used in hospitalized pts undergoing rapid immunomodulating therapy
--- _Stress dosing_ may be needed
- **Immunomodulators** - if CI or not controlled w/ corticosteroids
3. rapid immunomodulators - Effects last 3-6 wks
- **Plasmapheresis**
- **IVIG**
4. surgery - **Thymectomy** - May result in complete remission
36
dosing for pyridostigmine
1. Onset - 15 to 30 minutes
1. Duration - 3-4 hours
1. Dosing is patient dependent:
- often dosed 3-4x daily
- dosed **before meals** or **other activities that result in muscle fatigue**
- may be dosed later in the day depending on when symptoms begin
37
indications for rapid immunomodulating therapy
* Myasthenic crisis
* Pre-op tx in MG - helps prevent post-op “crisis”
* Bridging to slower acting immunotherapy
* Assist in maintaining remission in MG who are not well controlled on other tx
38
indications for thymectomy in MG
1. thymoma on imaging
1. No thymoma
- young patient
- +/- AChR ab
- generalized MG
- disabling ocular MG
39
management plan for Mild-Moderate Generalized MG
1st symptomatic therapy
chronic immunomodulating therapy if remains uncontrolled
40
management plan for Severe generalized or rapidly progressing MG
rapid immunomodulating + chronic immunomodulating + symptomatic
41
management plan for ocular MG
1. Symptomatic + chronic immunologic pharm
1. Thymectomy if indicated
1. Adjunct sx therapy for _ptosis_
- **Ptosis crutches/eyelid adhesive strips** - ensure adequate corneal lubrication by using lubricating drops and periods of abstinence from device
2. Adjunct sx therapy for _diplopia_
- **unilateral eye patch, opaque contact lens or eyeglass lens occlusion**
3. Refer to ophthalmology for **surgical intervention** for ptosis & diplopia
- _Indicated if stable ptosis or ophthalmoparesis_
42
management for refractory MG
Patients who do not respond well to symptomatic and standard chronic immunomodulating therapy may benefit from **monthly IVIG**
43
management for myasthenic crisis
1. admission to **ICU w/ ventilation assistance** as needed
1. **Rapid immunotherapy** bridging w/ **chronic immunotherapy**
- high dose glucocorticoids preferred if no CI due to short onset of clinical effect
44
pt ed for MG
1. **Avoid excessive chewing**
1. **Thicken liquids** to prevent nasal regurgitation or aspiration
1. **Remain physically active w/ frequent rests** but avoid sustained physical activity
1. **Education on myasthenic crisis** and **develop a written plan of care** for the patient to follow if this occurs
1. Educate pts to **avoid medications that can worsen MG**
1. _Women of childbearing age_
- **discuss teratogenicity** of meds and increased risk of birth defects in children born to MG mothers
45
An _inherited_ group of progressive myopathic disorders resulting from **defects in a number of genes required for normal muscle function** (w/o central or peripheral nerve abnormality) characterized by _progressive muscle weakness and wasting_
Categorized by mode of inheritance, age at onset, and clinical features
Muscular Dystrophy
46
most well-known muscular dystrophy
Duchenne and Becker Muscular Dystrophies
47
what is Duchenne and Becker Muscular Dystrophies (DMD & BMD)
1. Genetic defect on short arm of **X chromosome**
- X-linked recessive disorder - **MC Males**
- **Defective protein dystrophin** - responsible for muscle fiber strength
1. _DMD_ - **reduced/absent dystrophin** = rapid muscle damage with early use and more severe s/s
1. _BMD_ - _dystrophin lvls may be normal_, but **protein is altered** (misshapen) yet still functional = **later onset & milder course** of disease than DMD
48
presentation of DMD
1. Onset - usually 2-3 yrs of age
2. Progressive weakness
- Difficulty running, jumping, walking up steps
- Affects _proximal muscles_
- Affects **LE** _before_ UE
- **Gower’s sign** - use hand support to push themselves upright when arising from floor
3. PE
- Unusual waddling gait, lumbar lordosis
- Pseudohypertrophy of calf
- Shortened achilles tendons
- Decreased or absent DTR
- Often varying degrees of mild cognitive impairment
49
Complications/Comorbidities of DMD
1. dilated cardiomyopathy (DCM) - cardiac arrhythmias
1. frequent bone fractures
1. progressive scoliosis
1. respiratory muscle weakness
1. most patients are wheelchair bound by age 12
50
presentation of BMD
1. Less severe mutation results in less severe disease
2. **_Later onset, milder clinical s/s_** than DMD
- cognitive deficit is less and muscle weakness is less severe
- **able to ambulate at least until age 15** and commonly into adult life
- retained strength allows for clinical distinction between BMD and DMD
- **cardiac complications more evident** in BMD > DMD d/t retained ability to exercise
51
work up for Muscular Dystrophy
1. **_Serum CK_** - elevated prior to clinical signs
- peaks age 2, usually >10-20x ULN, then falls over 3-4 yrs
- increased in DMD/BMD carriers but lesser extent (3x ULN)
- _normal CK = r/o disease_
52
primary care management for muscular dystrophy
1. Refer to neuromuscular specialist/_muscular dystrophy center_ for confirmation of dx and multidisciplinary tx
- Specialists involved in care: neurology, cardiology, orthopedics, pulmonology, genetic counselor, dietician, psychiatry
53
how to confirm musclar dystrophy disease
1. **Genetic analysis - 1st line**, confirms dx in majority of cases
2. Muscle bx - _Rarely used_
- muscle cell degeneration, regeneration, isolated "opaque" hypertrophic fibers, replacement of muscle by fat and CT
- _Dystrophin analysis_
--- Normal pts have easily detectable dystrophin
--- DMD - most have total/near-total absence (< 5% of normal quantity) of dystrophin
--- BMD - 20-50% normal level (mild-mod), 5-20% normal level (severe)
54
mainstay therapy for musclar dystrophy
**Glucocorticoids** (*prednisone*)
* Decreases inflammation and influence repair of weakened muscle cell membranes - Provides significant _improvement in muscle strength, cardiac and pulm function_
* Stress dosing might be needed during periods of high physical/mental stress
* Monitor for SE of long-term therapy
55
genetic therapy for musclar dystrophy
**_Eteplirsen_** (Exondys 51)
1. induces new dystrophin protein expression in patients who have a gene mutation = **exon 51 skipping**
1. Indicated only for DMD patients with specific gene mutation
1. EMB outcome
- increased walking performance
- **increased dystrophin** on muscle bx
**_Golodirsen & Vitolarsen_**
1. induces new dystrophin protein expression in patients who have a gene mutation = **exon 53 skipping**
1. Indicated only for DMD patients with specific gene mutation
**_Casimersen_**
1. induces new dystrophin protein expression in patients who have a gene mutation = exon 45 skipping
1. Indicated only for DMD pts with specific gene mutation
1. EMB outcome
- increased walking performance
- increased dystrophin on muscle bx
_Delandistrogene moxeparvovec_
1. genetic therapy that introduces code on how to **create microdystrophin** which works similar to dystrophin but is smaller in size
1. **For ambulatory boys with DMD ages 4-5 years**
1. FDA approved based upon increase in microdystrophin production in two small trials
1. **benefit has not yet been established**
56
cardiac management in musclar dystrophy
1. **steroids may reduce new-onset and progressive cardiomyopathy**, lower deaths related to heart failure
1. **ARB/ACEI beginning at age 10** to reduce progression of heart failure
1. **Echo** _yearly at onset_ and **cardiac MRI** _yearly after age 7_
57
pulmonary management in musclar dystrophy
1. Use of CPAP at night can be used to treat symptomatic nocturnal hypoventilation
1. Early and aggressive treatment of lower respiratory infections
1. Maintain immunizations
58
bone health management in muscle dystrophy
1. **steroids reduce risk of scoliosis** and prolong independent ambulation
1. **increase risk of osteoporosis** and long bone & vertebral compression fractures
1. Prevention of osteoporosis
- Consider **calcium & vitamin D** supplementation
- **IV bisphosphonates** if compression fracture of vertebra; PO bisphosphonates controversial (CI if unable to sit/stand upright for 30 minutes)
- **PT & exercise**
1. Orthotics and leg braces
1. Surgical release of contractures
59
mental health management in musclar dystrophy
1. routine **neuropsych eval** for developmental, emotional or behavioral delays are necessary at each visit
1. referral to **psychiatrist/psychology** if needed
1. recommend **support groups, summer camps**
60
Advanced planning and palliative care in muscle dystrophy
1. discuss long term prognosis with patient/family
1. gently discuss treatment options, advanced care planning, advanced directive, palliative care
1. DMD
- improvement w/ tx seen between 3-6 y/o followed by gradual but relentless deterioration
- wheelchair confinement by age 12
- avg life span is mid 30’s (much improved from previous years due to advancements in care)
2. BMD
- remain ambulatory until mid-teens and often adulthood
- avg life span is mid 40’s
- **MCC of death is HF** from DCM
61
spectrum of disorders caused by a specific **mutation** in one of several **myelin genes** (> 80 genes affected) = **defects in myelin structure**, maintenance, and formation
Charcot-Marie-Tooth (CMT)
62
MC type of hereditary neuropathy
CMT
63
what type of mutation(s) can happen in CMT
a variety of mutations exist ranging from **point mutations** to **whole gene deletions/duplications**
64
CMT is MC in who?
1. **autosomal dominant inheritance**
- often a **strong FHx**
- May be sporadic, recessive, or X-linked
2. **Male** to female ratio of 3:1
65
presentation of CMT
1. Onset - 1st-3rd decade of life with **slow, progressive, distal leg weakness**
- _LE_ before UE
2. LE
- foot drop - inability to dorsiflex
- pes cavus - high arch and hammer toes
- foot deformities or gait disturbances are noted during childhood or early adult life
- weakness = atrophy
- Atrophy of muscles below knee
--- “inverted champagne bottle legs” or “stork leg deformity”
--- Hx of frequent sprained ankles, “clumsy”, trips easily
3. UE
- **hand weaknes**s presents with poor finger control, poor _handwriting, difficulty using zippers and buttons_, and clumsiness in _manipulating small objects_
- **claw hand**
4. Diminished/absent **DTRs**
5. Diminished **proprioception** and **vibration sense**
- _do not complain of subjective sensory sx_
1. **Sensory gait ataxia and (+) Romberg** d/t lack of distal sensation
1. +/- tremor
1. +/- palpable enlargement of peripheral nerves - noted late in disease
66
work up for CMT
1. Electrodiagnostic Studies: **EMG/NCS**
- **confirms evidence of neuropathy**
- if negative for neuropathy reconsideration of diagnosis is needed
2. **_Genetic testing - confirms the dx_** of CMT (after electrodiagnostics)
- less invasive but expensive
- genetic counseling for all pts/family w/ suspected hereditary neuropathy
67
tx for CMT
**_Supportive_**; no specific disease-modifying therapy
1. _PT_
- **daily stretching** exercises early in disease course may help delay contracture development
- **Non-weight-bearing exercise**
2. _Ankle-Foot Orthotics (AFO)_ - help stabilize ankles
3. _Orthopedic foot surgery_ - treat the pes cavus deformity and hammer toes
- Often needed between 10-20 years of age
68
Meds to avoid in CMT
metronidazole, nitrofurantoin, fluoroquinolones, amiodarone, colchicine
due to their **neurotoxic** potential
69
prognosis and monitoring for CMT
1. Slow progression that eventually leads to disability
1. Often live full life span but may have impaired quality of life
1. Disease exacerbation can occur in pregnancy
Monitoring
1. _Screen periodically for conditions that can exacerbate neuropathy_
- DM
- vitamin deficiencies
- immune-mediated neuropathies
70
MC DM complication
Diabetic Neuropathy
71
MC cause of peripheral neuropathy in developed countries
DM
72
how does diabetic neuropathy happen?
Neuropathy develops because of long-standing, poorly controlled DM
morphologic **abnormalities of the vasa nervorum** are present early in the course of the disease
73
3 types of diabetic neuropathy
1. Distal symmetric polyneuropathy
1. Isolated peripheral neuropathy
1. Autonomic neuropathy
74
MC form of diabetic peripheral neuropathy
Due to _axonal neuropathy_ - long nerves esp vulnerable
Distal symmetric polyneuropathy
75
presentation of Distal symmetric polyneuropathy
1. **Sensory sx** appear 1st in **stocking-glove pattern** - Bilateral, symmetric - dulled perception of vibration, pain, temp, light touch
2. Decreased/absent **ankle DTR** followed by widespread loss of reflexes
3. **Calluses & ulcerations** in high pressure areas (metatarsal heads) results from:
- Denervation of small muscles of foot
- Clawing of toes and displacement of submetatarsal fat pads
- Increased plantar pressures and decreased pain
- Repetitive stress (e.g. walking)
76
management for distal symmetric polyneuropathy
1. Strict glycemic control in all patients
1. Pharmacologic options
- _TCA_: **amitriptyline** (Elavil)
- _SNRI_: **duloxetine** (Cymbalta)
- _Anticonvulsants_: **pregabalin** (Lyrica) or **gabapentin** (Neurontin)
77
Least common of the diabetic neuropathies - seen mostly in older patients
Secondary to vascular ischemia or trauma
Isolated peripheral neuropathy
78
presentation of Isolated peripheral neuropathy
Only _mononeuropathy or mononeuropathy multiplex_
1. Often involves **CN (III,IV,VI) or femoral nerves**
- diplopia, pain/weakness in the distribution of the involved nerve
- Sudden onset with recovery in 6-12 wks of most or all function
2. **Diabetic amyotrophy** aka (lumbosacral radiculoplexus neuropathy)
- severe **pain in anterior thigh followed by weakness and quadriceps wasting** within a few days-weeks followed by improvement in pain
- Improves in 6-18 months
79
management for isolated peripheral neuropathy
same as distal symmetric polyneuropathy for analgesia + lidocaine patches
80
DM of long duration affects visceral functions (BP, HR, GI, bladder, ED)
what subtype of diabetic neuropathy?
Autonomic neuropathy
81
presentation of Autonomic neuropathy
1. GI dysfunction → N/V/C/D, early satiety, reflux, fecal incontinence
2. Bladder dysfunction - often leads to urine retention
3. orthostatis
4. ED
82
tx for GI dysfunction in autonomic neuropathy
1. Diarrhea
- broad spectrum abx (suspected bacterial overgrowth)
- loperamide (Imodium)
- diphenoxylate/atropine (Lomotil)
1. Constipation - increased fiber, fluids, stool softener, laxatives
83
tx for bladder dysfunction in autonomic neuropathy
1. **bethanechol (Urecholine)** - cholinergic agonist _increases detrusor muscle tone_
1. Alt: catheter decompression, surgical severance of vesical sphincter
84
tx for orthostatis in autonomic neuropathy
1. **compression stockings, tilting head of bed, arising slowly from supine position**
1. _Persistent sx despite conservative therapy_
- **fludrocortisone** (Florinef) - mineralocorticoid
- Alt: **midodrine** - alpha agonist
85
tx for ED in autonomic neuropathy
1. multifactorial: neurological, vascular and/or psychological
1. Tx - PDE-5 inhibitors - sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis)
1. May also try other non-pharmacologic ED treatments
86
Primarily an axonal neuropathy d/t chronic alcohol neurotoxicity
* sensory, motor, and autonomic
* more marked in legs than arms
Alcoholic Neuropathy
87
pathophys of Alcoholic Neuropathy
* Acetaldehyde, (a metabolite of ethanol), is neurotoxic
* Ethanol impairs axonal transport
* Complicated by demyelination d/t vitamin deficiency
88
presentation of Alcoholic Neuropathy
1. **Hx of chronic consumption of alcohol**
1. Insidious onset of distal lower extremity paresthesias, dysesthesias, or weakness
- MC presenting complaint is paresthesias of the feet and toes
- Progresses proximally and symmetrically
1. Generalized weakness +/- gait ataxia
1. Diminished or absent DTR
1. Altered sensory exam (touch, vibration)
89
management of alcoholic neuropathy
1. Supportive; specific tx not available
1. Physical and occupational therapy
1. Improved nutrition and cessation of drinking
1. Thiamine supplementation (thiamine deficiency is often coexisting)
1. Low doses of TCAs or gabapentin may help with dysesthesia
90
**Thiamine** pyrophosphate is the biologically active form of thiamine and functions as a ____
coenzyme in carbohydrate metabolism
91
a deficiency of thiamine pyrophosphate
beriberi
92
Exogenous thiamine is water-soluble, found in mostly where?
animal and plant tissues
Best sources - unrefined cereal grains, wheat germ, yeast, soybean flour, and pork
93
RF for thiamine deficiency
1. **Chronic alcohol abuse**, recurrent vomiting, TPN, bariatric surgery, inappropriately restrictive diets
- common in underdeveloped countries in populations who have limited access to an adequate diet
94
presentation subtypes of thiamine deficiency
1. **Dry beriberi** - symmetric peripheral _sensorimotor neuropathy_, loss of reflexes
- occurs in pts who are **inactive and have a low caloric intake**
- _“Wernicke-Korsakoff Syndrome”_: when CNS involvement occurs
--- **Wernicke encephalopathy** - nystagmus progressing to ophthalmoplegia, truncal ataxia and confusion
--- **Korsakoff syndrome** - amnesia, confabulation and impaired learning impairment
95
how to dx thiamine deficiency
1. Diagnostic testing is not necessary prior to treatment in an emergency setting
- Ex: pt presenting to ED with Wernicke-Korsakoff Syndrome
2. _Direct thiamine levels_ - normal 70 to 180 nmol/L
- can be assessed but may be **falsely reduced during systemic inflammation**
3. _Thiamine loading test_ - most reliable test (but not readily available)
- assess **erythrocyte transketolase activity** (ETKA) before and after administration of thiamine pyrophosphate (TPP)
- Expected results: **increase ETKA by 10-25%** after administration of thiamine
4. _Nerve Conduction Study_ - axonal sensorimotor polyneuropathy
96
management for thiamine deficiency
1. **Thiamine replacement** until proper nutrition is restored
- IV or IM, 50 - 100 mg/d, followed by oral dosing of 5-10 mg/d
2. neurology if evidence of Wernicke-Korsakoff Syndrome
97
A lack of Vit B 12 results in ?
damage to the myelin sheath
98
MCC of B12 deficiency
Pernicious anemia
Other causes:
* Diet (vegetarian/vegan)
* Gastrectomy or gastric bypass²
* IBD
* Pancreatic insufficiency
* H2 blockers and PPIs³
* Bacterial overgrowth
* Malabsorptive diseases (elderly)
* ETOH
99
presentation of B12 deficiency
1. **Paresthesias** of the hands followed by LE
1. **Sensory changes** - diminished proprioception, vibration, DTR’s
1. Unsteady gait → **sensory ataxia**
1. **Anemia** - fatigue, pallor, shortness of breath
1. Red swollen tongue or angular cheilitis ( **glossitis**)
- complaints of tongue discomfort, change in taste
1. Optic atrophy
1. Behavioral changes in severe cases
- mild irritability - dementia/ psychosis
100
how to dx of B12 deficiency
1. Confirm with **reduced serum cobalamin (B12) levels**
1. May order CBC
- 40% of pts - no anemia or macrocytosis
2. Pernicious anemia
- _Intrinsic factor ab_ - 60% of pts
- _Antiparietal cell ab_ - 90% of pts
3. NCS → axonal sensorimotor neuropathy (often not needed)
101
tx for B12 deficiency
various regimens of cobalamin
1. Standard regimen - 1000 mcg cyanocobalamin IM/wk x 1 mo, then 1000 mcg/mo
- does not completely reverse manifestations
102
Polyneuropathy may occur following ____ for ulcer, cancer, weight loss
Associated with rapid, significant weight loss and recurrent, protracted vomiting
gastric surgery
103
Initial manifestations of Neuropathy Associated with Gastric Surgery are ?
numbness and paresthesias in the feet
104
management for Neuropathy Associated with Gastric Surgery
1. **parenteral vitamin supplements, esp thiamine**
- improves w/ supplementation, parenteral nutritional support, and reversal of surgical bypass
