Anatomic olfactory structural abnormalities in congenital smell loss: magnetic resonance imaging evaluation of olfactory bulb, groove, sulcal, and hippocampal morphology.

BACKGROUND AND PURPOSE: There are 2 groups of patients with congenital smell loss: group 1 (12% of the total), in which patients exhibit a familial smell loss in conjunction with severe anatomical, somatic, neurological, and metabolic abnormalities such as hypogonadotropic hypogonadism; and a larger group, group 2 (88% of the total), in which patients possess a similar degree of smell loss but without somatic, neurological, or anatomical abnormalities or hypogonadism. Both groups are characterized by similar olfactory dysfunction, and both have been reported to have absent or decreased olfactory bulbs and grooves, which indicates some overlap in olfactory pathophysiology and anatomy. The purpose of this study was to evaluate patients with congenital smell loss, primarily among group 2 patients, comparing brain magnetic resonance imaging (MRI) results in patients with types of hyposmia. METHODS: Forty group 2 patients were studied by measurements of taste (gustometry) and smell (olfactometry) function and by use of MRI in which measurements of olfactory bulbs, olfactory sulcus depth, olfactory grooves, and hippocampal anatomy were performed. Anatomical results were compared with similar studies in group 1 patients and in 22 control subjects with normal sensory function. RESULTS: Olfactometry was abnormal in all patients with no patient reporting ever having normal olfaction. No patient had a familial history of smell loss. On MRI, all exhibited at least 1 abnormality in olfactory system anatomy, including absence or decreased size of at least 1 olfactory bulb, decreased depth of an olfactory sulcus, and abnormalities involving hippocampal anatomy with hippocampal malrotations. One patient had bilateral bulb duplication. Normal subjects with normal smell and taste function exhibited some but very few or significant neuroanatomical changes on MRI. CONCLUSIONS: Although both groups have similar abnormalities of smell function, group 2 patients demonstrate anatomical anomalies in olfactory structures that are neither as common nor as severe as in group 1 patients. Group 2 patients can have a wide range of olfactory anatomical abnormalities.

Taste and smell function in chronic disease: a review of clinical and biochemical evaluations of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC.

PURPOSE: To describe systematic methods developed over 40 years among over 5000 patients at The Taste and Smell Clinic in Washington, DC to evaluate taste and smell dysfunction. MATERIALS AND METHODS: A tripartite methodology was developed. First, methods to determine clinical pathology underlying the multiple disease processes responsible for taste and smell dysfunction were developed. Second, methods to determine biochemical parameters responsible for these pathologies were developed. Third, methods to implement these techniques were developed to form a unified basis upon which treatment strategies can be developed to treat these patients. RESULTS: Studies were performed in 5183 patients. Taste loss was present in 62% of patients, smell loss in 87%. Most patients with taste loss (52%) exhibited Type II hypogeusia; most patients with smell loss (56%) exhibited Type II hyposmia. Sensory distortions were present in 60%. Four common diagnostic entities were found: post influenza-type hyposmia and hypogeusia (27% of patients), idiopathic causes (16%), allergic rhinitis (15%) and post head injury (14%). Regardless of clinical diagnosis the major biochemical abnormality found in most patients (~70%) was diminished parotid salivary and nasal mucus secretion of cAMP and cGMP. CONCLUSIONS: Taste and smell dysfunctions are common clinical problems associated with chronic disease processes. These symptoms require a systematic, integrated approach to understand their multiple and complex components. The approach presented here can and has led to effective treatment.

Neuroimaging of a pilocytic astrocytoma with anaplastic features and diffusion tensor imaging characteristics.

We report the MRI findings of an adult patient with a (rare in adults) biopsy-proven pilocytic astrocytoma with anaplastic features. Diffusion tensor imaging may potentially provide information on cell proliferation, vascularity, and fiber destruction, which can have implications for treatment and prognosis. In this case, tractography and fractional anisotropy maps demonstrated displacement of adjacent parenchyma and relatively intact fractional anisotropy, suggesting a pilocytic rather than an anaplastic astrocytoma.

Dysembryoplastic neuroepithelial tumor with atypical presentation: MRI and diffusion tensor characteristics.

We report the neuroimaging findings of a 26-year-old female patient with a biopsy-proven dysembryoplastic neuroepithelial tumor (DNET). DNETs are an uncommon, usually benign, glial-neural cortical neoplasm of children and young adults who typically present with intractable seizures. DNETs may occur in any region of the supratentorial cortex, but have a predilection for the temporal lobes. Accurate neuroimaging diagnosis is essential since patients with DNET benefit from complete resection. However, accurate differentiation from other cortical lesions may be challenging. Typical conventional Magnetic Resonance Imaging (MRI) features can help in the differentiation from other similar cortical tumors. Diffusion tensor imaging can also provide important additional diagnostic information regarding the degree of involvement of adjacent parenchyma and white matter tracts. In this case, tractography and fractional anisotropy maps demonstrated that fiber tracts surrounding the lesion were displaced, but fiber integrity was maintained, which is more suggestive of a DNET rather than a more aggressive neoplasm. Accurate identification of DNETs is essential for the purpose of rendering a timely diagnosis and start appropriate treatment.

Olfactory Hallucinations without Clinical Motor Activity: A Comparison of Unirhinal with Birhinal Phantosmia.

Olfactory hallucinations without subsequent myoclonic activity have not been well characterized or understood. Herein we describe, in a retrospective study, two major forms of olfactory hallucinations labeled phantosmias: one, unirhinal, the other, birhinal. To describe these disorders we performed several procedures to elucidate similarities and differences between these processes. From 1272, patients evaluated for taste and smell dysfunction at The Taste and Smell Clinic, Washington, DC with clinical history, neurological and otolaryngological examinations, evaluations of taste and smell function, EEG and neuroradiological studies 40 exhibited cyclic unirhinal phantosmia (CUP) usually without hyposmia whereas 88 exhibited non-cyclic birhinal phantosmia with associated symptomology (BPAS) with hyposmia. Patients with CUP developed phantosmia spontaneously or after laughing, coughing or shouting initially with spontaneous inhibition and subsequently with Valsalva maneuvers, sleep or nasal water inhalation; they had frequent EEG changes usually ipsilateral sharp waves. Patients with BPAS developed phantosmia secondary to several clinical events usually after hyposmia onset with few EEG changes; their phantosmia could not be initiated or inhibited by any physiological maneuver. CUP is uncommonly encountered and represents a newly defined clinical syndrome. BPAS is commonly encountered, has been observed previously but has not been clearly defined. Mechanisms responsible for phantosmia in each group were related to decreased gamma-aminobutyric acid (GABA) activity in specific brain regions. Treatment which activated brain GABA inhibited phantosmia in both groups.

Morphological changes of olfactory bulbs and grooves: initial report of supernumerary olfactory bulbs.

BACKGROUND: Observations and measurements of olfactory structures in humans have been difficult and not of common neuroradiological interest. Because of our interest in olfaction, we have studied the presence, size, and function of these structures in normal subjects and in patients with smell loss. METHODS: Magnetic resonance imaging studies of brain were performed in 220 consecutive patients in our medical center for a variety of clinical neurological investigations. Magnetic resonance imaging studies were performed in each subject including high-resolution coronal T2-weighted fast-spin echo images in the orbitofrontal region. Measurements of olfactory bulb diameter, olfactory sulcal depth, and morphology of the olfactory grooves were performed. RESULTS: Olfactory bulbs were present bilaterally in each patient studied. Olfactory bulbs appeared duplicated in 11 patients and triplicated in one (5.4% of the total group). Whereas olfactory sulcal depth was similar in all patients, olfactory bulb diameter in patients with duplicate or triplicate bulbs was significantly smaller than those in subjects with single bilateral olfactory bulbs. One patient with congenital hyposmia and olfactory bulb duplication had significant impairment in olfactory acuity. None of the other subjects complained of smell loss. CONCLUSIONS: Olfactory bulbs with a duplicated or triplicated appearance and associated changes in olfactory groove morphology can be present in patients examined with orbital magnetic resonance imaging, and are not uncommon. Although the mechanism(s) for this finding is unclear, it may relate to neurodevelopmental and genetic factors.

Neuroimaging of tumefactive multiple sclerosis with atypical features.

Tumefactive demyelinating lesions or tumefactive multiple sclerosis (TMS) constitute a unique presentation of demyelinating disease that frequently mimics intracranial neoplasm, infection or other, nondemyelinating intracranial pathology. Consequently, these lesions, which are larger than typical multiple sclerosis plaques and are generally characterized by certain MRI features including edema and incomplete ring enhancement, pose a serious diagnostic challenge that frequently prompts biopsy in initial evaluation. Biopsy can be averted when imaging features for TMS are seen on MRI. We present a biopsy-proven case of TMS with atypical imaging features, evaluated using MRI and diffusion-tensor imaging.

Narrowing of Meckel's cave and cavernous sinus and enlargement of the optic nerve sheath in Pseudotumor Cerebri.

OBJECTIVE: Pseudotumor cerebri (PTC) is a clinical entity of uncertain etiology associated with several subtle findings on magnetic resonance imaging (MRI) including posterior flattening of the globes, enlargement of the optic nerve sheath (ONS), empty sella sign. We aimed to characterize the incidence of and significance of 2 novel MRI findings: narrowing of Meckel's cave and of cavernous sinus. METHODS: Forty-six patients with a condition diagnosed as PTC based on clinical history were retrospectively reviewed, and their MRI studies were assessed for previously reported imaging findings associated with PTC. The maximal diameters of the cavernous sinuses, Meckel's caves, and ONSs were measured along with those of age-matched controls on axial T2-weighted images. RESULTS: The Meckel's caves and cavernous sinuses are significantly (P < 0.01) narrowed in patients (mean diameters: 0.41 and 0.25 cm) versus controls (0.54 and 0.36 cm), respectively. The ONS was enlarged in patients with a mean diameter of 0.65 cm versus 0.54 cm (P < 0.01). Meckel's cave narrowing and ONS enlargement seem to be better indicators of PTC than cavernous sinus narrowing, with sensitivities of 78.3% and 86.9% and specificities of 84.8% and 76.1% versus 60.9% and 76.1%, respectively. CONCLUSIONS: This finding of narrowed Meckel's caves in PTC may be clinically useful as a novel imaging finding seen on routine MRI studies. Optic nerve sheath enlargement is also confirmed as an important finding in PTC.

Improvement in smell and taste dysfunction after repetitive transcranial magnetic stimulation.

BACKGROUND: Olfactory and gustatory distortions in the absence of odors or tastants (phantosmia and phantageusia, respectively) with accompanying loss of smell and taste acuity are relatively common symptoms that can occur without other otolaryngologic symptoms. Although treatment of these symptoms has been elusive, repetitive transcranial magnetic stimulation (rTMS) has been suggested as an effective corrective therapy. OBJECTIVE: The objective of the study was to assess the efficacy of rTMS treatment in patients with phantosmia and phantageusia. METHODS: Seventeen patients with symptoms of persistent phantosmia and phantageusia with accompanying loss of smell and taste acuity were studied. Before and after treatment, patients were monitored by subjective responses and with psychophysical tests of smell function (olfactometry) and taste function (gustometry). Each patient was treated with rTMS that consisted of 2 sham procedures followed by a real rTMS procedure. RESULTS: After sham rTMS, no change in measurements of distortions or acuity occurred in any patient; after initial real rTMS, 2 patients received no benefit; but in the other 15, distortions decreased and acuity increased. Two of these 15 exhibited total inhibition of distortions and return of normal sensory acuity that persisted for over 5 years of follow-up. In the other 13, inhibition of distortions and improvement in sensory acuity gradually decreased; but repeated rTMS again inhibited their distortions and improved their acuity. Eighty-eight percent of patients responded to this therapeutic method, although repeated rTMS was necessary to induce these positive changes. INTERPRETATION: These results suggest that rTMS is a potential future therapeutic option to treat patients with the relatively common problems of persistent phantosmia and phantageusia with accompanying loss of taste and smell acuity. Additional systematic studies are necessary to confirm these results.

Orbital plasmablastic lymphoma with remission following chemotherapy.

We report the case of a middle-aged HIV-positive man who presented with proptosis and retro-ocular pain. On CT and MR imaging, a retro-orbital enhancing mass was seen, and PET/CT revealed this lesion as well as a similarly characterized mass in the nasopharynx to be hypermetabolic. Biopsy and subsequent pathological characterization revealed this mass to be plasmablastic lymphoma (PBL), a rare form of non-Hodgkin's lymphoma associated with HIV-infection. PBL is a diffuse B-cell lymphoma with characteristic cell marker patterns. The most common site of this malignancy is within the oral cavity. This case constitutes an unusual orbital manifestation of plasmablastic lymphoma as well as an unusual case in its response to chemotherapy. This case illustrates the importance of functional imaging with PET/CT in the diagnosis, management, and follow-up of plasmablastic lymphoma.

Carbonic anhydrase I, II, and VI, blood plasma, erythrocyte and saliva zinc and copper increase after repetitive transcranial magnetic stimulation.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used to treat symptoms from many disorders; biochemical changes occurred with this treatment. Preliminary studies with rTMS in patients with taste and smell dysfunction improved sensory function and increased salivary carbonic anhydrase (CA) VI and erythrocyte CA I, II. To obtain more information about these changes after rTMS, we measured changes in several CA enzymes, proteins, and trace metals in their blood plasma, erythrocytes, and saliva. METHODS: Ninety-three patients with taste and smell dysfunction were studied before and after rTMS in an open clinical trial. Before and after rTMS, we measured erythrocyte CA I, II and salivary CA VI, zinc and copper in parotid saliva, blood plasma, and erythrocytes, and appearance of novel salivary proteins by using mass spectrometry. RESULTS: After rTMS, CA I, II and CA VI activity and zinc and copper in saliva, plasma, and erythrocytes increased with significant sensory benefit. Novel salivary proteins were induced at an m/z value of 21.5K with a repetitive pattern at intervals of 5K m/z. CONCLUSIONS: rTMS induced biochemical changes in specific enzymatic activities, trace metal concentrations, and induction of novel salivary proteins, with sensory improvement in patients with taste and smell dysfunction. Because patients with several neurologic disorders exhibit taste and smell dysfunction, including Parkinson disease, Alzheimer disease, and multiple sclerosis, and because rTMS improved their clinical symptoms, the biochemical changes we observed may be relevant not only in our patients with taste and smell dysfunction but also in patients with neurologic disorders with these sensory abnormalities.

Bilateral and independent Broca areas confirmed by Wada test and functional magnetic resonance imaging.

Accurate preoperative evaluation of language dominance is critical when evaluating potential patients for temporal lobe epilepsy surgery. Although most people have left-sided language dominance, a minority of patients have been described with either bilateral or right hemispheric dominance. We present a patient with right temporal lobe epilepsy who presented with bilateral and functionally independent Broca areas, as confirmed by Wada testing and functional magnetic resonance imaging.

Brain gamma-aminobutyric acid changes in stiff-person syndrome.

BACKGROUND: Patients with stiff-person syndrome (SPS) have circulating antibodies against glutamic acid decarboxylase, the rate-limiting enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA). Although the patients' symptoms of stiffness and unexpected spasms can be explained on the basis of reduced or impaired inhibitory neurotransmitters, such as GABA, it is unclear whether the level of GABA in the brains of these patients is reduced and, if so, whether the reduction is due to anti-glutamic acid decarboxylase antibodies. OBJECTIVE: To measure GABA levels in the brains of patients with SPS. DESIGN: Prospective case-control study. SETTING: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md. PATIENTS: Eight patients with SPS with high titers of circulating anti-glutamic acid decarboxylase antibodies and typical clinical symptoms of SPS and 16 control subjects. MAIN OUTCOME MEASURES: Results of brain magnetic resonance imaging and magnetic resonance spectroscopy, which measures GABA levels in specific brain regions. RESULTS: No abnormalities were noted on brain magnetic resonance images. A prominent and significant decrease in GABA level was, however, observed in the sensorimotor cortex and a smaller decrease in the posterior occipital cortex but not in the cingulate cortex or pons. CONCLUSIONS: The reduction of brain GABA in patients with SPS supports the clinical symptoms and indicates that the inhibitory GABAergic pathways are involved in the disease. Regardless of the responsible autoantigens, in SPS autoantibodies block the function of GABAergic neurons and interfere with the synthesis of GABA but do not cause structural changes in the brain.

Brain gamma-aminobutyric acid levels are decreased in patients with phantageusia and phantosmia demonstrated by magnetic resonance spectroscopy.

BACKGROUND: Olfactory and gustatory hallucinations (phantosmias and phantageusias, respectively) are sensory distortions that commonly follow losses of olfactory and gustatory acuity (hyposmia and hypogeusia, respectively). The biochemical basis of these hallucinations is unclear. Functional magnetic resonance imaging has been used previously to demonstrate widespread and robust central nervous system (CNS) activation to memories of these sensory distortions in patients with these symptoms. In this study, possible CNS mechanisms responsible for these distortions were evaluated using magnetic resonance spectroscopy, because this technique has been used to measure various CNS metabolites in patients with neurologic disorders. METHODS: Forty-seven subjects were studied: 28 normal volunteers (13 men and 15 women) and 19 patients (8 men and 11 women) with persistent oral global phantageusia and/or birhinal phantosmia studied before any treatment. Four patients (1 man and 3 women) were studied before and after pharmacologic treatment that reduced the severity of their sensory distortions. All subjects were studied in a Signa 1.5-T magnetic resonance scanner with a quadrature head coil using a modified standard 2-dimensional J-point resolved excitation in the steady state (PRESS) sequence by which gamma-aminobutyric acid (GABA), glutamic acid, choline, N-acetylaspartate, and creatine (Cre) were measured in various CNS regions. Results were expressed using Cre as a denominator to determine ratios for each measurement. Differences were defined between normal subjects and patients before treatment and in patients before and after successful pharmacologic treatment. RESULTS: Before treatment, GABA levels in several CNS regions were lower in patients than in normal volunteers and were the only biochemical changes found; significantly lowered GABA levels were found in the cingulate, right and left insula, and left amygdala. No differences between patients and normal volunteers were found in any of the metabolites in the posterior occipital region. After treatment that inhibited sensory distortions, CNS GABA levels increased in the cingulate, insula, and amygdala but significantly only in the left insula and in the right and left amygdala. After this successful treatment, no change in any biochemical parameter was found in the posterior occipital region. CONCLUSIONS: These results indicate that decreased brain GABA levels can serve as biochemical markers of phantageusia and/or phantosmia in patients with these distortions and are the first biochemical changes in the CNS that reflect these sensory changes. After successful treatment of these distortions, CNS GABA levels increased to levels at or near normal, consistent with functional remission of these symptoms. These results substantiate a role for CNS GABA in the generation and inhibition of these sensory hallucinations. Although the underlying biochemical mechanism(s) for the generation of these decreased GABA levels are complex, because similar types of sensory hallucinations occur as auras or prodromata of epileptic seizure and migraine activity, these results suggest that there may be common biochemical changes among these disorders.

Rapid modulation of GABA in sensorimotor cortex induced by acute deafferentation.

Recovery of function after acute injury to the central nervous system may be controlled by the availability of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the cerebral cortex. Acute lesions as well as manipulation of sensory inputs can lead to rapid reorganization of the cerebral cortex, occurring within minutes to hours. Reduction of cortical inhibitory tone through a decrease in the availability of GABA has been suggested as a possible mechanism; however, the degree and temporal course of the changes in brain GABA are not known. A novel method using two-dimensional J-resolved magnetic resonance spectroscopy showed that GABA levels in the human sensorimotor cortex are quickly reduced within minutes of deafferentation. This finding strongly supports the view that the release of latent corticocortical projections from tonic inhibition through decreased GABA availability is a mechanism of rapid cortical plasticity. Reduction of brain GABA can play a pivotal role in regulating the extent of rapid cortical reorganization after lesions or changes in sensory input.