Numbness, Tingling, and More
Simon Oh, M.D.
Colorado Neurology Center
4/10/2015
Approach to Neuropathy
History
 “Listen to the patient. He is trying to tell you what is
wrong with him.”
- Sir William Osler
Approach to Neuropathy
History
 “Listen to the patient. He is trying to tell you what is
wrong with him…
 Unless the patient has everything checked positive
on a 14-point review of systems.”
- Sir Simon Oh
Approach to Neuropathy
History
 nature of the complaints
 sensory or motor or both?
 distribution
 mononeuropathy?
 multiple mononeuropathies?
 symmetric polyneuropathy?
 time course
 acute onset or insidious onset?
 rapid progression or slow progression?
 associated symptoms
Location
• “just like real estate”
– location, location, location
Clinical Approach
Neurological Examination
 cranial nerves
 motor
 strength
 tone
 muscle bulk
 reflexes
 sensory
 modalities
 distribution
 coordination
 gait
Clinical Approach
Sensory Pattern
 Dermatomal distribution?
Clinical Approach
Sensory Pattern
 Nerve distribution?
Clinical Approach
Motor Unit
 What part of the motor unit is involved?
Clinical Approach
Motor Unit
 What part of the motor unit is involved?
 Motor neuron disease?
 Radiculopathy?
 Neuropathy?
 Neuromuscular junction?
 Myopathy?
Case 1
Simon Oh, M.D.
Colorado Neurology Center
History
The patient is a 66-year-old right-handed woman who
has had falling problems over the past 2 years. She first
fell about 2 years ago. She was in a hurry and she thinks
that she may have tripped. She almost dropped her
grandchild, but was able to break her fall. She ended up
tearing her right rotator cuff which required surgery.
Since September 2014, she has been falling more
frequently. No dizziness or prodrome. No focal
weakness. She thinks that she may trip or stumble. The
falling does not occur on a daily basis, but occurs
frequently. She has had 4 significant falls and she may
have rolled her right ankle once.
History
She has mild numbness and tingling in her feet.
No burning. She has balance problems. When
rinsing her hair in the shower, she sometimes
has to hold onto the wall for balance. She has
occasional muscle cramps, but no focal
weakness.
She has been diabetic for about 15-20 years.
Her last hemoglobin A1c was ~6.0%.
Past Medical History
1.
2.
3.
4.
5.
diabetes mellitus
hypertension
gastroesophageal reflux disease
restless leg syndrome
gout
Medications
1.
2.
3.
4.
5.
6.
7.
allopurinol 300 mg daily
aspirin 81 mg at night
losartan 50 mg daily
metformin 500 mg twice daily
omeprazole 20 mg daily
ropinirole 2 mg at night
supplements include glucosamine
Allergies/Adverse Reactions
1. pregabalin
2. statins, including atorvastatin
Social History
•
•
•
•
married
originally from Canada
rare alcohol use
no tobacco or illicit drug use
Family History
•
no family history of any neurological disorders
ROS
•
•
•
•
•
•
•
•
•
•
•
•
•
•
General: No fevers or chills. No fatigue or weakness. No weight change.
Eyes: No blurred vision or double vision. No eye pain.
ENT: No hearing loss or ringing in the ears. No nosebleeds. No hoarseness or dysphagia.
Cardiovascular: No chest pain or palpitations. She has leg swelling.
Respiratory: No asthma, chronic cough, or shortness of breath.
GI: No nausea or vomiting. No diarrhea or constipation.
Genitourinary: No blood in urine. No dysuria or incontinence.
Musculoskeletal: No lower back or neck pain. No arthritis. She has muscle cramping. No
fasciculations.
Skin: No rashes currently. No nail changes or hair changes.
Neurologic: No headaches. No seizures. No history of stroke. No speech problems. She
has numbness or tingling. No memory loss. No loss of consciousness.
Psychiatric: No depression or anxiety. No insomnia. No hallucinations.
Endocrine: She has diabetes mellitus. No history of thyroid disorder.
Hematologic/lymphatic: No bleeding, bruising, or lymph node swelling.
Allergies/immunologic: No hay fever. She has had a drug rash to statins.
Physical Exam
Vitals: Wt= 154 lbs.
Ht= 5’0”
BP= 118/74
HR= 71
RR= 20
General: She is well groomed, well appearing, and in no acute distress.
HEENT: Normocephalic and atraumatic. No scleral icterus. No conjunctival injection. No ptosis
or lid lag. Mucous membranes are moist and the oropharynx is clear.
Cardiovascular: Regular, rate, and rhythm. 2+ pedal pulses.
Respiratory: Non-labored.
Musculoskeletal: Full range of motion. No joint deformities. No clubbing or cyanosis.
Skin: No rashes. The skin in the lower extremities is dry. There is some hyperemia in the toes
and soles of the feet. Normal skin turgor.
Psychiatric: She is euthymic and makes good eye contact. Thought is linear.
Hematologic/Lymphatic/Immunologic: No peripheral edema in the lower extremities.
Neuro Exam
Mental Status: She is alert and has a clear sensorium. Speech is fluent. No dysarthria.
Cranial Nerves: Pupils are equal, round, and reactive to light. Extraocular movements are intact with
smooth pursuit and no nystagmus. Visual fields are full to confrontation. There is normal facial
sensation to light touch and good strength in the muscles of mastication. There is no facial asymmetry
or weakness. Hearing is intact to finger rubs bilaterally. The soft palate elevates symmetrically and
uvula is midline. There is normal strength in the trapezius and sternocleidomastoid muscles bilaterally.
The tongue is midline with appropriate strength.
Motor: 5/5 strength in all proximal and distal muscle groups of all 4 extremities. Muscle tone is
normal throughout with no cogwheeling or spasticity. There is no muscle atrophy.
Reflexes: 2+ biceps, brachioradialis, and triceps reflexes. 1+ patellar and absent ankle reflexes.
Sensation: Sensation is intact to light touch throughout. Vibration is decreased in the toes compared
to the fingers. A Romberg sign is present.
Coordination: Finger-to-nose is normal bilaterally with no tremor or dysmetria.
Gait: The gait is normal with normal arm swing.
Diagnosis?
Evaluation
• laboratory testing
• EMG/nerve conduction study
Evaluation
At the initial visit, there was clinical evidence
of a peripheral neuropathy. Laboratory
testing to look for other etiologies for
peripheral neuropathy were ordered. Her
B12 level was low at 225. SPEP did not show
a monoclonal protein. ESR was normal at
2.0. Her TSH was slightly high at 5.90.
EMG/NCS
 small myelinated fibers (Ad) and unmyelinated C fibers
are not assessed by the nerve conduction study
 despite extensive evaluation, the etiology of a
peripheral neuropathy may be unknown in 25-50% of
the cases
 technical factors
Nerve Conduction Study
Electromyography
EMG/NCS
• The EMG/nerve conduction study showed
evidence of a length-dependent sensory
and motor polyneuropathy.
EMG/NCS
Left Sural SNAP
Left Superficial Peroneal SNAP
EMG/NCS
Left Peroneal CMAP
Left Tibial CMAP
EMG/NCS
Left Radial SNAP
Discussion
• diabetic polyneuropathy
– most common cause of peripheral neuropathy in
Western countries
– 8% had neuropathy at the time of diagnosis
– 50% had neuropathy after 25 years
– risk factors:
•
•
•
•
•
glycemic control
hypertension
smoking
obesity
high triglycerides
Discussion
• diabetic polyneuropathy
– distribution
• usually symmetric with a length-dependent
pattern
– sensory and motor
• injury to nerve axons
• initially the toes are affected with numbness and
tingling with a slow progression proximally
• ~10% report pain (burning, stabbing, or shooting
Discussion
• diabetic polyneuropathy
– autonomic features
•
•
•
•
•
autonomic instability
erectile dysfunction
bladder dysfunction
gastroparesis
sweating abnormalities
Discussion
• B12 deficiency
– cofactor for methionine synthase and 1methylmalonyl-coenzyme A mutase
– can lead to axonal loss and some demyelination in
peripheral nerves
– can cause dorsal column damage in the spinal cord
• hypothyroidism
– associated with a length-dependent sensory
polyneuropathy
– large-fiber modalities are decreased
– decreased reflexes
Discussion
• iatrogenic causes
– metformin
• B12-intrinsic factor complex uptake is calcium
dependent
• metformin affects calcium-dependent membrane
action
– allopurinol
• may cause a sensory neuropathy
Follow Up
She was started on a low dose of thyroid
medication by her PCP. She was also put on
B12 injections. She was put on alpha lipoic
acid. She has not had any further falls. The
paresthesias are better.
Case 2
Simon Oh, M.D.
Colorado Neurology Center
History
The patient is a 24-year-old woman with no significant past
medical history who has had intermittent lower back pain for the
past 2 years. Her achy pain ranges between 5-7/10 in intensity.
The pain is exacerbated with high-impact workouts, as well as
flexion at the hip. She has gotten some improvement with
massage and a lower back injection. No focal weakness in her
lower extremities. No muscle cramps or fasciculations. No bowel
or bladder dysfunction. She has some mild numbness on the
bottom of her feet. The numbness has been occurring for more
than 2 months. There were no antecedent illnesses, such as
diarrhea or a respiratory infection.
She underwent MRI of the lumbar spine without contrast on
7/2/2014 that showed mild degenerative disc disease at L5-S1.
Past Medical History
• none
Medications
1. diclofenac as needed
2. methocarbamol as needed
Allergies
• NKDA
Social History
•
•
•
single
rare alcohol use
no tobacco or illicit drug use
Family History
• no family history of any neurological disorders
Physical Exam
Vitals: Wt= 126 lbs.
Ht= 5’4”
BP= 110/80
HR= 71
RR= 20
O2 sat= 98% RA
General: She is well groomed, well appearing, and in no acute distress.
HEENT: Normocephalic and atraumatic. No scleral icterus. No conjunctival injection. No
ptosis. Mucous membranes are moist and the oropharynx is clear.
Cardiovascular: Regular, rate, and rhythm. 2+ radial and pedal pulses.
Respiratory: Non-labored.
Musculoskeletal: Full range of motion. No joint deformities. No clubbing or cyanosis.
Skin: No rashes, lesions, or ulcers. The skin in the lower extremities is not dry. There is
hyperemia in the toes of the feet. Normal skin turgor.
Psychiatric: She is euthymic and makes good eye contact. Thought is linear.
Hematologic/Lymphatic/Immunologic: No peripheral edema in the lower extremities.
Neuro Exam
Mental Status: She is alert and has a clear sensorium. Speech is fluent. No dysarthria.
Cranial Nerves: Pupils are equal, round, and reactive to light. Extraocular movements are intact with
smooth pursuit and no nystagmus. Visual fields are full to confrontation. There is normal facial
sensation to light touch and good strength in the muscles of mastication. There is no facial asymmetry
or weakness. Hearing is intact to finger rubs bilaterally. The soft palate elevates symmetrically and
uvula is midline. There is normal strength in the trapezius and sternocleidomastoid muscles bilaterally.
The tongue is midline with appropriate strength. No tongue fasciculations.
Motor: 5/5 strength in all proximal and distal muscle groups of all 4 extremities. Muscle tone is
normal throughout with no cogwheeling or spasticity. There is no muscle atrophy.
Reflexes: Absent biceps, brachioradialis, triceps, patellar, and ankle reflexes.
Sensation: Sensation is intact to light touch throughout. Vibration is decreased in the toes compared
to the fingers. A Romberg sign is present.
Coordination: Finger-to-nose is normal bilaterally with no tremor or dysmetria.
Gait: The gait is normal with normal arm swing.
Diagnosis?
Evaluation
• EMG/nerve conduction study
– electrodiagnostic findings consistent with a
demyelinating peripheral neuropathy, such as
chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP)
EMG/NCS
Right Sural SNAP
Right Superficial Peroneal SNAP
EMG/NCS
Right Peroneal CMAP
Right Tibial CMAP
Chronic Inflammatory
Demyelinating
Polyradiculoneuropathy (CIDP)
• an acquired immune-mediated
neuropathy with demyelinating features
• characterized by progressive sensory loss
and weakness, affecting proximal and
distal limbs
Typical CIDP
• chronically progressive, stepwise, or
recurrent symmetric proximal and distal
weakness and sensory dysfunction in all
extremities
• > 2 months duration
• cranial nerves may be affected
• reduced or absent DTRs
Atypical CIDP
• chronically progressive, stepwise, or recurrent in
nature
–
–
–
–
–
predominantly distal
asymmetric
focal
pure motor
pure sensory
• > 2 months duration
• reduced or absent DTRs (may be normal in
unaffected limbs
Epidemiology
• rare
– affects ~3-8/100,000
– may be underdiagnosed
• males more affected
– male: female ratio is 2:1
• age
– affects patients of all ages
– average age is ~50s
Epidemiology
• can occur with concurrent illness
–
–
–
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diabetes mellitus
HIV infection
connective tissues disorders
thyrotoxicosis
monoclonal gammopathy of undermined significance
chronic hepatitis
liver transplantation
lymphoma
melanoma
carcinoma
Evaluation
• EMG/nerve conduction study
– conduction blocks
• any drop in CMAP amplitude of 20%
– temporal dispersion
• any increase in CMAP duration of >15%
Evaluation
• laboratory testing
– CSF protein may be elevated with a normal WBC count
• MRI
– may show enhancement or enlargement of nerve roots
• nerve biopsy
Treatment
• IVIG
• plasmapheresis
• steroid therapy
Follow Up
An EMG/nerve conduction study on 7/26/2014 and it was
markedly abnormal due to the presence of diffuse
slowing, temporal dispersion, and absent/markedly
delayed F-responses. It was felt that she had CIDP. She
travelled to Mayo Clinic where the diagnosis was
confirmed. She began IVIG in early August 2014. She got
2 g/kg divided over 4 days. She had maintenance doses
of 1 g/kg over 1 day. She got headaches and flu-like
symptoms after her treatments. She felt like she had
gotten weaker and she had been falling. She still had
numbness in her legs. She was empirically put her on
B12 injections and she felt much better on the daily and
weekly doses.
Follow Up
On a follow up evaluation on 9/18/2014, she had 5/5
strength in all proximal and distal muscle groups of the
upper extremities except she had 4-/5 strength with hip
flexion and ankle dorsiflexion. She could not stand from a
crouched position. Muscle tone was normal throughout.
There was no muscle atrophy. Her gait was abnormal
due to a steppage gait.
Follow Up
On a follow up evaluation on 11/29/2014, she had 5/5
strength in all proximal and distal muscle groups of the
upper extremities except she had 4-/5 strength with hip
flexion and 2/5 with ankle dorsiflexion. She could not
stand from a crouched position. Muscle tone was normal
throughout. There was no muscle atrophy. Her gait was
very abnormal due to a significant steppage gait. A
follow up EMG/NCS showed progressive worsening of
demyelination.
Follow Up
IVIG therapy was stopped. She was put on prednisone 60
mg daily. 4 weeks later, she had 5/5 strength with hip
flexion and 4-/5 with ankle dorsiflexion. She could stand
from a crouched position. Muscle tone and bulk were
normal throughout. Her gait was better, but still slow
compared to her normal baseline. She was started on
methotrexate 15 mg weekly with folic acid. Over the next
2 months, her prednisone was decreased slowly to 10 mg
daily.
Case 3
Simon Oh, M.D.
Colorado Neurology Center
History
The patient is a very pleasant 31-year-old right-handed woman with a
Chiari I malformation who underwent decompression in June 2011.
Prior to her surgery, she had weakness in her limbs. She states that she
developed weakness in her left hand during her freshman year in
college. At that time, she had problems with typing and holding
objects. She essentially developed a left wrist drop. She then
developed a wrist drop and weakness in her right upper extremity. She
did not have any visual disturbances or dysphagia. She was worked up
by a another neurologist. She had an “abnormal” EMG/NCS. She
apparently also had a muscle biopsy of a left wrist flexor in 2005 and
the results were not clear. In the last year and a half, she developed a
right foot drop followed by weakness of her left ankle. She has mild
numbness and tingling intermittently in her forearms and legs. She has
some fasciculations when she is tired. She also has some mild tremors
in her hands.
Past Medical History
1. Chiari I malformation
2. s/p Chiari decompression surgery in June 2011
3. history of C-sections in 2007 and 2010
Medications
1. Reclipsen oral contraception as directed
Allergies
• NKDA
Social History
•
•
•
married
1-2 glasses of wine weekly
no tobacco or illicit drug use
Family History
• no family history of any neurological disorders or
muscle disease
Physical Exam
Vitals: Wt= 113 lbs.
Ht= 5’2”
BP= 98/68
HR= 86
RR= 16
O2 sat= 99% RA
General: She is well groomed, well appearing, and in no acute distress.
HEENT: Normocephalic and atraumatic. No scleral icterus. No conjunctival injection. No
ptosis. Mucous membranes are moist and the oropharynx is clear.
Cardiovascular: Regular, rate, and rhythm. 2+ radial pulses.
Respiratory: Non-labored.
Musculoskeletal: Full range of motion. No joint deformities. No clubbing or cyanosis.
Skin: No rashes. The skin in the lower extremities is not dry. There is no hyperemia in the toes
and soles of the feet. Normal skin turgor.
Psychiatric: She is euthymic and makes good eye contact. Thought is linear.
Hematologic/Lymphatic/Immunologic: No peripheral edema in the lower extremities.
Neuro Exam
Mental Status: She is alert and has a clear sensorium. Speech is fluent. No dysarthria.
Cranial Nerves: Pupils are equal, round, and reactive to light. Extraocular movements are intact with
smooth pursuit and no nystagmus. Visual fields are full to confrontation. There is normal facial
sensation to light touch and good strength in the muscles of mastication. There is no facial asymmetry
or weakness. Hearing is intact to finger rubs bilaterally. The soft palate elevates symmetrically and
uvula is midline. There is normal strength in the trapezius and sternocleidomastoid muscles bilaterally.
The tongue is midline with appropriate strength. There are no fasciculations or wasting of the tongue.
Motor: 4+/5 strength in the deltoids and biceps bilaterally. 5-/5 strength in the triceps bilaterally. 4-/5
with wrist flexion. 3/5 strength with wrist extension and interossei muscles. There is decreased
muscle bulk in the wrist extensors in her forearms. 5/5 strength with hip flexion, hip
adduction/abduction, knee flexion/extension, and ankle plantarflexion bilaterally. 3/5 strength with
ankle dorsiflexion bilaterally. There is decreased muscle mass in the extensor digitorum brevis and
abductor hallucis muscles. She has decreased bulk in the anterior tibialis muscles. Tone is slightly
decreased. There is no cogwheeling or spasticity. There is no clinical myotonia. No fasciculations are
seen on examination.
Neuro Exam
Reflexes: 1+ biceps, brachioradialis, triceps, patellar, and ankle reflexes. There is no percussion
myotonia with percussion of the thenar muscles or the wrist extensors. Plantar responses show
downgoing toes bilaterally. Hoffmann’s signs are not present bilaterally.
Sensation: Sensation is intact to light touch throughout. Vibration is decreased in the toes compared
to the fingers. A Romberg sign is unequivocally present.
Coordination: Finger-to-nose shows no dysmetria. There is a terminal tremor bilaterally.
Gait: There is a mild steppage gait with both legs.
Evaluation
• laboratory testing
– 2-hour fasting glucose tolerance test, TSH, SPEP,
and ESR were within normal limits
– B12 was on the lower side of normal at 315
– anti-GM1 Abs were negative
• EMG/nerve conduction study
– electrodiagnostic findings showed a
polyneuropathy, motor with conduction block,
demyelinating and axonal
– all sensory nerves were normal
EMG/NCS
Right Sural SNAP
EMG/NCS
Right Peroneal CMAP
Right Tibial CMAP
EMG/NCS
Right Peroneal CMAP
Right Tibial CMAP
EMG/NCS
Right Radial SNAP
EMG/NCS
Left Median CMAP
Left Ulnar CMAP
EMG/NCS
Left Radial CMAP
Right Radial CMAP
Diagnosis?
Multifocal Motor Neuropathy
(MMN)
• an acquired immune-mediated neuropathy
with demyelinating features
• characterized by progressive asymmetrical
weakness with no sensory involvement
• restricted to signs of lower motor neuron
disease
–
–
–
–
weakness
wasting
fasciculations
absent or reduced reflexes
Epidemiology
• rare
– affects ~1/100,000
• males more affected
– male: female ratio is 3:1
• age
– affects patients from 20-80
– average age is ~40s
Clinical Presentation
• progressive weakness
– distal muscles usually affected first
• wrist drop
• foot drop
• asymmetrical presentation
– rare to have cranial nerve involvement or respiratory
involvement
• insidious and slow
• other symptoms
– muscle cramps and fasciculations
– no sensory involvement
Examination
• weakness
–
–
–
–
–
radial nerve
median nerve
ulnar nerve
musculocutaneous nerve
peroneal nerve
• reflexes
– reduced
– no plantar responses or clonus
Findings
• laboratory testing
– anti-GM1 Abs
• EMG/NCS
– conduction blocks
• any drop in CMAP amplitude of 20%
Follow Up
An EMG/nerve conduction study on 4/3/2012 was markedly
abnormal due to the presence of conduction blocks in a number
of motor nerves. All sensory nerves were completely normal. It
was felt that she had MMN.
Follow Up
She began IVIG in early May 2012. She got 2 g/kg divided over 5
days. She then had maintenance doses of 1 g/kg over 2 days.
Follow Up
The patient continues to get better. On 12/18/2014, she had 5/5
strength with neck flexion and extension. 5/5 strength in the
deltoids, biceps, and triceps bilaterally. 5-/5 with wrist flexion. 4/5 strength with wrist extension and interossei muscles. 5/5
strength with her finger flexors. There was decreased muscle
bulk in the wrist extensors in her forearms. 5/5 strength with hip
flexion, hip adduction/abduction, knee flexion/extension, and
ankle plantarflexion bilaterally. 4-/5 strength with right ankle
dorsiflexion and eversion. 5-/5 strength with left ankle
dorsiflexion and eversion. There was decreased muscle mass in
the extensor digitorum brevis and abductor hallucis muscles.
Tone was slightly decreased. There was no cogwheeling or
spasticity. Her gait was improved with less steppage.
Questions?