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Paroxysmal Dystonia with Axonal Neuropathy Resulting from Benignant Insulinoma: Case Report

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Authors:  Nicolò Gabriele Pozzi MD, Roberto De Marzi MD, Roberta Zangaglia MD, Brigida Minafra MD and Claudio Pacchetti MD

Article first published online:  24 FEB 2015 | DOI: 10.1002/mdc3.12123

Case Report

In February 2013, a Caucasian 29-year-old man was evaluated because of a complex choreodystonic syndrome characterized by abrupt onset of paroxysmal involuntary movements.

In June 2010, he began to present multiple episodes of abnormal behavior-like panic attacks, as well as paraesthesia-like and “inside tremor” sensations with increasing anxiety, occurring during both day and night, without a specific trigger. He worsened over months, developing recurrent motor symptoms described as sudden, involuntary, uncoordinated movements of arms, legs, or the whole body, occurring alone or in clusters and lasting from a few minutes up to half an hour, with or without consciousness impairment. Over the years, they worsened in extent and their frequency increased, from one in a month to two to three times per week. “Intercritical” periods were asymptomatic.

Physical examinations, brain CT scans, blood exams, EEGs, and MRIs, performed from 2010 to 2013, showed no pathological findings.

In 2012, after psychiatric indication, he was treated, for an overall 6-month period, with antidepressant and -psychotic therapy (citalopram, lorazepam, amisulpiride, and olanzapine). Because no clinical benefit was achieved, the patient discontinued the treatments by himself.

Familial and previous medical history were unremarkable; he only reported a 6-kg weight gain since 2010. He was well integrated in his community and worked as a policeman until January 2013, when he was temporarily discharged for medical reasons.

In February 2013, after a first outpatient medical examination, he was hospitalized for further evaluation. The patient documented his symptoms with an extensive homemade video collection recorded by his wife. The emerging clinical picture can be summarized as a complex choreodystonic syndrome characterized by episodes of multifocal, segmental, or generalized dystonia, dystonic tremor, multifocal jerky movements, or generalized ballistic movements happening alone or in clusters (see Video 1). At neurological examination, only a mild segmental strength loss (4+) in both quadriceps was found. Routine blood test, thyroid-stimulating hormone, free T4, and neoplastic markers were normal, except for blood glucose value, which was 17 mg/dL (Table 1A). Blood samples were retested, confirming this finding, although he was completely asymptomatic. Suspecting the presence of an insulinoma, a panel of exams was scheduled.

Table 1. Patient's value of both blood and liquor tests
  Patient Value Normal Values
  1. Insulin values were normal, compared to the general population, but because of the subject's low glucose level, they represented a severe relative hyperinsulinemia. This severe condition was not duplicated in CSF, because the patient was already treated (diazoxide 50 three times daily, while waiting for surgery), at the time of CSF tests.

  2. IgG, immunoglobulin G.

(A) Blood samples analyses
Blood tests
Blood glucose 17 70–105 mg/dL
Blood insulin 13.6 2.6–24.9 mU/mL
Postprandial blood insulin 27.4 2.6–24.9 mU/mL
C-peptide 4.9 ng/mL (0.9–4.0)
Blood insulin/C-peptide 2.77 >1.0
(B) CSF samples analyses
CSF test
Glucose (liquor) 35 50–80 mg/dL
Glucose (blood) 67 65–115 mg/dL
Glucose (liquor/blood) 52% >45%
Lactic acid (liquor) 1.1–2.4
Albumin (liquor) 40 10–30 mg/dL
Albumin (blood) 3818 3,700–5,100 mg/dL
Transferred albumin ratio (liquor/blood) 1.1% <0.7%
IgG (liquor) 4.7 1.4–4.0 mg/dL
IgG (blood) 1,036 690–1,400 mg/dL
IgG index 0.43 <0.70
Q lim IgG 8.4  
IgG ratio 4.5 <QlimIgG
IgG loc 0 0
Cytometry <2 <2

Insulin blood level, c-peptide, and postprandial glucose level were tested (Table 1). Abdominal CT identified a clear round and capsulated tumefaction (2 cm in diameter) in the toe of the pancreas (Fig. 1), highly suggestive of a benign neoplastic formation. Presence of metabolic damages to the peripheral nervous system (PNS) was investigated by nerve conduction study and needle electromyography that revealed axonal motor polyneuropathy in all four limbs. Central nervous system (CNS) involvement was also investigated by cerebrospinal fluid (CSF) testing, EEG, brain MRI, and a neuropsychological evaluation, which failed to find significant alterations.

 CT image shows, pointed up by the arrow, the pancreatic neoformation during artery phase.Figure 1. CT image shows, pointed up by the arrow, the pancreatic neoformation during artery phase. Dimensions are reported in the left side.

The patient underwent a laparoscopic distal pancreatectomy. The tumor (2.5 × 1.5 cm in size) was histologically analyzed and classified as a benign islet cell adenoma.



The patient's clinical picture was at first interpreted as psychogenic paroxysmal dyskinesias (PxDs), although main diagnostic features suggesting a functional ethiology were missing.[1] Owing to the absence of specific triggers and to the attack's duration, PxDs resulting from PRRT2 gene mutations might have been considered in our case, given the duration of attacks, lack of nonkinesigenic triggers, and mixed choreodystonic phenomenology.[2] However, given the negative familial history and the age at onset, it is mandatory to exclude secondary forms of paroxysmal movement disorders (PMDs). Indeed, several conditions, most of them treatable, may cause PMDs, such as hypoparathyroidism, pseudohypoparathyroidism, and cerebrovascular diseases. Hypoglycemia is a rare cause of PMD and can be caused by an insulinoma (sporadic or within a multiple endocrine neoplasia [MEN] syndrome)[3] or by a paraneoplastic syndrome.[4]Given its insidious nature, this condition is still a diagnostic challenge. Detecting a low glucose level may be difficult because of the erratic activity of neoplastic cells, so serial samples analyses should be performed. Hypoglycemic condition, even if asymptomatic (hypoglycemia unawareness), is highly suggestive for insulinoma.[5] Once suspected, CT scan remains the investigation of choice, confirming the presence of neoplastic tissue, localizing the site of surgery, and helping in differential diagnoses between sporadic cases and MEN syndrome.[3] Given the high rate of success, patients should be referred to surgery, when contraindicated oral therapy remains a suitable option.[3]

In conclusion, our final diagnosis was paroxysmal dystonic-dyskinetic syndrome and axonal motor neuropathy resulting from insulinoma. The complete remission of neurological symptoms after the tumor's excision strongly supports the correlation between both PNS and CNS symptoms and impaired glucose metabolism.[6-10] Genetic progress is improving our understanding in PMD, but formulating a proper presumptive diagnosis remains an essential requirement. An accurate anamnestic and symptoms record, and a high grade of suspect and several observations are crucial to pursue the recognition of this diagnostically challenging condition.


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