Acopeds.org

Title: Pandysautonomic Neuropathy Presents as Fatigue, Generalized Neuropathic Pain,
and Dysphagia in a 15-Year-Old Female
Author(s):
Binh Phung, DO1; Travis Campbell, DO1; Shawna Duncan, DO1; Joseph Walter, MD2; Michael Chang, MD3; and David Siegler, MD4

Affiliation(s): 1 Oklahoma State University Department of Pediatrics, Tulsa, Oklahoma
2 Pediatric Pulmonology – The Children’s Hospital at Saint Francis, Tulsa, OK
3 Pediatric Infectious Disease – The Children’s Hospital at Saint Francis, Tulsa, OK
4 Pediatric Neurology – Child Neurology of Tulsa LLC, Tulsa, OK
ABSTRACT BODY

Background: The syndrome of acute pandysautonomia was first reported in 1969 and
described as the development of autonomic dysfunction with relative or complete preservation
of somatic motor/sensory functions. The features of this disorder may involve both the
sympathetic and parasympathetic divisions of the autonomic nervous system
(pandysautonomia). Initial nonspecific symptoms of fatigue, headache, and generalized
neuropathic pain are followed by autonomic symptoms including orthostatic hypotension, light-
headedness, blurry of vision, dry eyes, cold feet/hands, reduced or accentuated sweating,
abdominal pain, diarrhea, dysphagia, gastroparesis, and defects in micturition stream and/or
volume. A prodrome of febrile or viral illness may precede the onset of pandysautonomia
neuropathy. The symptoms may evolve over a few days or weeks, but may be more gradual in
onset. Autonomic neuropathies may present as a feature of an autoimmune-mediated
peripheral neuropathy with the presence of specific autoantibodies. Moreover, it has also been
reported in association with infectious mononucleosis, streptococcus, coxsackie B virus, rubella,
herpes simplex virus, and other viral syndromes.
Objective: To review the clinical case presentation of a patient who presents with symptoms
consistent with pandysautonomic neuropathy.
Design/Methods: Clinical case presentation.

Results: 15-year-old previously healthy Caucasian female presents with a 6-day history of
fatigue, fever, and worsening generalized back pain. She was seen on three occasions at
various ER/urgent care facilities and was treated with IM/oral antibiotics for urinary tract
infection, oral analgesia (Lortab, Tylenol with codeine), and steroids. At a follow-up visit with her
PCP, she had “blurry of vision with unequal pupils” and was subsequently referred to an
ophthalmologist who diagnosed her with asymmetric tonic pupils (the right pupil being minimally
responsive to light). She was then admitted for further evaluation. During the admission, she
developed voiding dysfunction, throat pain/dysphagia, constipation followed by non-bloody
diarrhea, and diffuse skin dysesthesias associated with generalized myalgias from the neck
down (sparing her head). She did not have any weakness and had intact neurologic reflexes.
She was able to ambulate with support. CT scans of the head, abdomen, and pelvis were all
negative. MRI of the lumbar and thoracic spine showed no abnormalities, aside from possible
right upper lobe infiltrate suggestive of aspiration. She then received a dysphagiagram due to
complaints of difficulty swallowing, which showed risk for aspiration of both solids and liquids.
Several days into the admission, she had unexplained desaturations requiring supplemental
oxygen, alongside episodes of orthostatic hypotension. A 2D-echo showed normal intracardiac
anatomy. She was evaluated by neurology and psychiatry, without any clear diagnoses.
Infectious disease was consulted, who alluded to an autoimmune process stemming from an
underlying rheumatologic disorder. Due to the lack of rheumatology subspecialty, she was
transferred to another Children’s Hospital where she was evaluated by GI, general surgery,
neurology, infectious disease, hematology/oncology, rheumatology, urology, and pain
specialists. Per GI, she was found to have esophageal dilatation with significant dysmotility of
the gastrointestinal tract. In addition, she had an abnormal gastric emptying study. A
nasojejunum (NJ) tube was temporarily placed for supplemental nutrition and erythromycin was
initiated for gastroparesis. She was evaluated by general surgery who recommended
gastrojejunal (GJ) tube placement for enteral nutrition, but her parents declined the surgery.
With respect to her inability to swallow, anisocoria, and bladder dysfunction, neurology
diagnosed her with acute pandysautonomic neuropathy. She received IV immunoglobulin, as
well as a short course of acyclovir. Infectious disease sent for additional lab tests including CSF
studies for cryptococcus, Bartonella, syphilis, HSV-1 & 2, HIV, enterovirus, coxsackie B, West
Nile virus, tick titers, parvovirus B19, cryoglobulins, and Legionella, which were reportedly all
negative. Heavy metal panel including lead, mercury, arsenic, cadmium, chromium was
negative. Due to the orthostatic hypotension, she was started on Mestinon (pyridostigmine) and
Florinef (fludrocortisone). She was initially started on a significant high dose of IV steroids, but it
was tapered by hematology/oncology secondary to a complication of possible autoimmune
hemolytic anemia. Rheumatology obtained inflammatory markers (ESR, CRP), paraneoplastic
antibody panel (type 1 anti-neuronal nuclear antibody, Purkinje cell antibodies Type 2,
collapsing response mediator protein-5 antibodies), autoimmune tests (C-ANCA, P-ANCA, ANA,
RF, anti-Ro/SSA, anti-La/SSB), and neuronal nicotinic acetylcholine receptor antibodies, P/Q-
type Ca2+ channel antibodies, all of which were reportedly negative. She did test positive for
Ach-receptor antibody, but never had a follow-up EMG study for evaluation of myasthenia
gravis. She subsequently developed bladder dysfunction, which she now self-catheterizes 3
times daily per recommendations of urology. Her underlying diagnosis is still not clear, but
presumed to be autoimmune in nature. Her neuropathic pain was adequately treated with
Tramadol, Gabapentin, and Effexor. She was ultimately discharged in stable condition to follow-
up with nutrition, neurology, pulmonology, urology, and pain specialist. Her pupils have since
returned to baseline and are reactive to light/accommodation bilaterally. Of note, the patient has
had multiple subsequent hospitalizations due to sepsis, toxic colitis, and pneumonia/bronchitis
(with increased oxygen requirement) given the complicated course of pandysautonomic
neuropathy and its multi-organ involvement.
Conclusion: Pandysautonomic neuropathy manifestations may be the sole or predominant
feature of an acute (or subacute) peripheral neuropathy. The hallmark of these autonomic
neuropathies, in varying combinations, may include orthostatic hypotension, secreto-motor
paralysis, constipation, bladder dysfunction, impotence, and blurry of vision associated with
tonic pupils (as seen in this patient). An immune-mediated mechanism and/or viral syndrome
may be associated with acute autonomic and sensory neuropathy. Only about 40% of cases
recover fully to pre-morbid health status. For an estimated 12% of patients, symptoms persist
with significant complications involving other organ systems. Full or partial recovery may take
months to years. This rare but complicated condition requires a multidisciplinary approach to
provide the appropriate care for the patient.

Source: http://www.acopeds.org/ejacop/2013fall/docs/A5.pdf