Dysautonomia secondary to third ventriculostomy successfully managed with midodrine

Abstract

Hypothalamic lesions can compromise its essential regulatory roles resulting in critical disruption of temperature and blood pressure homoeostasis. We present the case of a 55-year-old woman who had been previously submitted to several neurosurgical procedures aimed at treating idiopathic hydrocephalus. She presented to our department with recurring episodes of hypothermia and wide blood pressure variations, which had been worsening over the last few years. After extensive complementary workup, which excluded new neurological lesions or endocrinological conditions, hypothalamic dysfunction was assumed to be the cause of this syndrome. She was successfully treated with midodrine and on-demand captopril, which resulted in adequate control of her blood pressure. This case highlights the rare and unpredictable consequences of damage to the hypothalamus, depicting the favourable result of a heretofore unpublished medical approach.

Background

The hypothalamus is the most important organ in maintaining body homoeostasis and its destruction is incompatible with life.¹ The ability to control homoeostasis relies on the coordination of endocrine, autonomical and behavioural responses, by integrating several sensorial and hormone inputs and through outputs towards the anterior and posterior hypophysis, cerebral cortex, pre and motor neurons and sympathetic and parasympathetic preganglionic neurons.¹

The influence of the hypothalamus on the autonomic functions has been studied for many years and many syndromes related to hypothalamic dysfunction are known. Dysautonomic syndromes can either be spontaneous or the result of specific mechanisms including trauma and iatrogenic brain injury.^{2 3}

These syndromes usually present in a dramatic manner, with extreme and paroxysmal variations of blood pressure, heart rate, respiratory rate, body temperature and diaphoresis.⁴

When hypothalamic lesions are present, their locations can correlate with symptoms, even though their size is not always proportional to their severity.⁵ It is known, for example, that ventromedial lesions can cause changes in caloric balance with ensuing hyperphagia and that lateral hypothalamic lesions can cause aphagia and weight loss.⁵ Damage to the anterior hypothalamus can cause hyperthermia, whereas damage to the posterior hypothalamus can lead to hypothermia, frequently with diaphoresis. Sleep abnormalities can also be present.⁵

As the thermoregulation centre is located in the hypothalamus, it is common that disturbances in this region result in hypothermia or hyperthermia, either sustained or paroxysmal. The thermal disregulation secondary to hypothalamic damage has been described in the context of several pathological processes such as tumours, trauma, ischemia, haemorrhage and so on.⁶ Cases of spontaneous hypothermia in patients with structural changes in the corpus callosum—Shappiro syndrome—are also described in the literature.⁷

Besides being the thermoregulation centre, the hypothalamus has a role in the regulation of blood pressure. The posterior region is responsible for the rise of blood pressure and heart rate through the inhibition of the baroreceptors and sympathetic constriction activity. Conversely, the anterior hypothalamus lowers heart rate and blood pressure.⁸

We present herein a particular case of chronic hypothalamic dysfunction following iatrogenic hypothalamic damage, which is a difficult to diagnose and treat condition.

Case presentation

A 55-year-old white woman was taken to the emergency department in August due to mental confusion and hypothermia (35°C). She had a history of wide blood pressure variations, hypothermia and diaphoresis since 2014, which had been worsening around 2016, leading to several previous hospital admissions. This patient was submitted in 2010 to the placement of a ventriculoperitoneal shunt (VPS) due to chronic triventricular hydrocephalus secondary to idiopathic stenosis of Sylvius aqueduct (figure 1) that caused progressive neurological impairment. Three months later, due to system malfunction, a revision of the distal portion of the shunt was done, creating a new abdominal path. Six months after VPS placement, the patient was again submitted to neurosurgery due to acute neurological symptoms. Endoscopic third ventriculostomy was then performed successfully (figure 2). In 2014, following the sudden onset of neurological signs, MRI revealed ventrigulomegaly affecting mainly the right lateral ventricle with secondary deviation of the septum pellucidum to the left, which was ultimately found during surgery to be caused by unilateral (right) Monro foramen obstruction (figure 3). Endoscopic venticulostomy was redone due to the obstruction of previous fenestration and unilateral foraminoplasty was performed, both were performed successfully. In this multiple surgery context, postsurgical syndrome of inappropriate antidiuretic hormone secretion ensued, which was managed successfully by restricting water intake. She also had a previous medical history of epilepsy since childhood and iatrogenic hypothyroidism following total thyroidectomy for toxic multinodular goitre in 2016. Her regular medication included levothyroxine 75 micrograms once daily (od), levetiracetam 1 g two times per day and lisinopril 5 miligrams od.

Figure 1.

MRI axial T2 Fluid-attenuated inversion recovery (FLAIR). Triventricular hydrocephalus secondary to idiopathic stenosis of Sylvius aqueduct.

Figure 2.

MRI sagittal T1 cut. Sylvius aqueduct stenosis.

Figure 3.

MRI, axial T2. Ventrigulomegaly affecting mainly the right lateral ventricle with secondary deviation of the septum pellucidum.

Investigations and differential diagnosis

In the course of admission for the etiologic study of this syndrome and symptom control, several episodes of hypothermia (minimum 34°C) and diaphoresis were registered. Furthermore, there was extreme tensional lability, with severe hypotension (minimum systolic pressure of 60 mm Hg) and hypertensive spikes (maximum of 190 mm Hg), which were neither triggered by posture nor any other traceable factor. The hypertensive episodes were accompanied with headache, flush, dizziness and anxiety. Routine blood work was unremarkable, with exception to hyponatremia, resolved after the adjustment of her anticonvulsant medication.

A head CT scan was performed showing right frontal subcortical and left periventricular sequelae lesions (figure 4). MRI was performed, showing two frontal trepanation holes right next to what was identified as corticosubcortical encephalomalacia with apparent bilateral ventricular paths. Leukoaraiosis was also described. Pituitary parenchymal expression was enlarged given her age, although no pathological meaning was attributed to the findings described in the Sella turcica (figure 5A, B). Abnormalities in the hypothalamus—hypophysis—adrenal gland axis blood tests were absent (adrenocorticotropic hormone, follicle-stimulating hormone, prolactin, luteinizing hormone, growth hormone within the normal range), except for high thyroid-stimulating hormone with normal T4 (interpreted in the setting of the patient’s known hypothyroidism with insufficient levotiroxin adjustment). Several arterial blood pressure monitoring examinations were performed, all revealing inconsistent and inconclusive results. A tilt test had been recently performed with a negative result. Urinary catecholamines, serum and urinary metanephrines, dopamine and 5-hydroxyindoleacetic acid levels were all within the reference range. Finally, a thyroid-stimulating hormone scintigraphy, together with all the previous lab results, definitely excluded the hypothesis of pheochromocytoma and paraganglioma.

Figure 4.

CT showing bifrontal lesions.

Figure 5.

(A) T2 coronal sections of the third ventricle. (B) MRI sagital T2 after third ventriculostomy.

Based on the aforementioned data, we presumed that the patient’s dysautonomia was related to hypothalamic dysfunction, with no manifest impairment of pituitary gland.

Treatment

An unsuccessful attempt at restoring proper blood pressure and body temperature control was made using fludrocortisone, which was then discontinued. Oral midodrine 2.5 mg qd was soon after initiated resulting in gradual satisfactory regulation of both blood pressure and body temperature. The dosage was later titrated to 15 mg, with sustained results. As these vital parameters became under control, there was a subsequent improvement of mental status, eventually settling the clinical manifestations that led to the patient’s admission.

Outcome and follow-up

One year after this episode, the patient shows no recurrence of hypothermia or hypotension, keeping the aforementioned midodrine regimen. Captopril is seldom taken PRN to control sporadical hypertensive crisis.

Discussion

This is a case of chronic dysautonomia after iatrogenic brain injury in which the symptoms observed can be explained by the lesions in the hypothalamus. Since the damage was mainly in hypothalamic regions,⁹ it can be assumed that thermoregulation was compromised, resulting in the recurrent episodes of hypothermia and diaphoresis. In addition to this, blood pressure regulation also seemed to be compromised, also in likely connection with the hypothalamic lesion.

Nevertheless, although it is known that structural lesions in or around the hypothalamus can induce chronic hypothermia,¹⁰ it is rare to find these manifestations in a subacute or chronic presentation, as it has been described. Very few of the already scarce reported cases of hypothermia following brain injury are associated with hypotension, as it was the case of our patient.^11–14

Tuettenberg et al,¹¹ Thorley et al¹³ and Kubota et al¹⁴ describe the cases of autonomic dysfunction after radiologically proven hypothalamic lesion, in individuals of varying ages, all of them presenting thermoregulation disorders, with no cardiovascular impairment.

On the other hand, and also given the rarity of hypotension associated with hypothalamic dysfunction, Popugaev et al¹⁵ conducted a study to help characterise the clinical syndrome of hypotension in patients after sella turcica removal surgery, concluding that the hypothalamic damage caused by immediate fluid resistance would be the only possible explanation for this clinical presentation.

Only De Tanti et al¹⁶ presented a case of autonomic dysfunction with disruption of thermal and blood pressure regulation, in a patient on a vegetative state after brain trauma.

The available literature mentions as possible pharmacological treatments for hypothalamic dysfunction, with varying degrees of success¹⁷: bromocriptine, dantrolene, cyproheptadine,¹⁸ clonidine,¹⁹ chlorpromazine,²⁰ oxybutynin,²¹ glycopyrrolate,²² carbamazepine²³ and clomipramine.^{24 25} Popugaev et al¹⁵ advocate the use of sympathomimetics for resistant arterial hypotension, as the decrease in vascular tone and relative hypovolemia are considered the main mechanisms. In our case, midodrine was the chosen drug, as it is recommended in cases of neurogenic orthostatic hypotension,²⁶ resulting in the successful achievement of blood pressure normalisation.

To the best of our knowledge, this is the first reported case of chronic autonomic dysfunction due to iatrogenic damage resulting in thermal and cardiovascular abnormalities in a patient with maintained neurocognitive function.

Learning points.

• Hypothalamic dysfunction can result from spontaneous phenomena or trauma injury, namely surgery.

• It presents typically with dysautonomia either cardiovascular, thermal or both.

• Midodrine can be successfully used as an effective treatment option as all the others previously described.